首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   348篇
  免费   26篇
  国内免费   7篇
儿科学   1篇
基础医学   87篇
口腔科学   7篇
临床医学   19篇
内科学   52篇
皮肤病学   6篇
神经病学   8篇
特种医学   27篇
外科学   17篇
综合类   35篇
预防医学   20篇
药学   90篇
中国医学   10篇
肿瘤学   2篇
  2023年   1篇
  2022年   6篇
  2021年   16篇
  2020年   17篇
  2019年   13篇
  2018年   7篇
  2017年   9篇
  2016年   10篇
  2015年   10篇
  2014年   15篇
  2013年   27篇
  2012年   19篇
  2011年   26篇
  2010年   27篇
  2009年   17篇
  2008年   24篇
  2007年   17篇
  2006年   16篇
  2005年   17篇
  2004年   11篇
  2003年   14篇
  2002年   5篇
  2001年   5篇
  2000年   5篇
  1999年   6篇
  1998年   5篇
  1997年   5篇
  1996年   2篇
  1995年   8篇
  1994年   3篇
  1993年   3篇
  1992年   2篇
  1991年   3篇
  1990年   1篇
  1988年   4篇
  1987年   1篇
  1986年   4篇
排序方式: 共有381条查询结果,搜索用时 31 毫秒
1.
The molecular properties of proteins are influenced by various ions present in the same solution. While site-specific strong interactions between multivalent metal ions and proteins are well characterized, the behavior of other ions that are only weakly interacting with proteins remains elusive. In the current study, using NMR spectroscopy, we have investigated anion–protein interactions for three proteins that are similar in size but differ in overall charge. Using a unique NMR-based approach, we quantified anions accumulated around the proteins. The determined numbers of anions that are electrostatically attracted to the charged proteins were notably smaller than the overall charge valences and were consistent with predictions from the Poisson–Boltzmann theory. This NMR-based approach also allowed us to measure ionic diffusion and characterize the anions interacting with the positively charged proteins. Our data show that these anions rapidly diffuse while bound to the proteins. Using the same experimental approach, we observed the release of the anions from the protein surface upon the formation of the Antp homeodomain–DNA complex. Using paramagnetic relaxation enhancement (PRE), we visualized the spatial distribution of anions around the free proteins and the Antp homeodomain–DNA complex. The obtained PRE data revealed the localization of anions in the vicinity of the highly positively charged regions of the free Antp homeodomain and provided further evidence of the release of anions from the protein surface upon the protein–DNA association. This study sheds light on the dynamic behavior of anions that electrostatically interact with proteins.

Biological systems involve various inorganic and organic ions. Protein functions are influenced by the surrounding ions not only through the electrostatic screening effect (1), but also through direct interactions at the molecular surfaces (2). Compared to typical protein–ligand interactions, protein–ion interactions are weaker and more transient, yet ions can significantly influence various properties such as solubility, stability, and functional activities of proteins (3). The influences depend on ionic species. For example, when Cl ions are replaced with glutamate ions in biochemical experiments, some DNA-binding proteins exhibit substantially stronger (>100-fold for some cases) affinity for DNA (4, 5). To understand how ions affect the molecular properties of proteins, the behavior of ions around proteins should be elucidated.For DNA and RNA, ion-counting methods have greatly advanced experiment-based knowledge of ionic interactions (6, 7). These methods were successfully used to examine and validate theoretical models for ion–nucleic acid interactions (8, 9). However, ion-counting methods do not provide any information about the spatial distribution and dynamic properties of counterions around macromolecules. Even at high resolution in crystal structures, the vast majority of counterions are unresolved, suggesting that they are highly mobile. The dynamic nature of ions causes a major difficulty in studying the interactions between ions and biological macromolecules.Weak transient interactions of monovalent ions with proteins are particularly difficult to capture by experiments. Unlike nucleic acids that possess a negative charge at every residue, proteins typically contain both positively charged and negatively charged residues as well as many neutral residues. Consequently, proteins possess a far smaller overall charge than nucleic acids of similar molecular size. This implies that the electrostatic attraction of ions to proteins could be intrinsically weaker than that to nucleic acids. Furthermore, local environments around individual charged moieties of proteins are more diverse compared to those of nucleic acids. Although NMR spectroscopy is powerful for investigating various physicochemical properties of proteins (10, 11), there has been a lack of methods suited to quantitatively investigate ion–protein interactions. Experimental studies of weak ion–protein interactions have been challenging (3).In this work, using unique experimental methods, we study how anions behave in the vicinity of proteins. Our NMR-based approach allows us to determine how many anions are attracted to proteins. Our data show that the number is significantly smaller than the overall charge valence of each positively charged protein. We explain this observation using the concept of the ion atmosphere and theoretical calculations based on the Poisson–Boltzmann equation. Our experimental approach also reveals the diffusional properties of anions interacting with proteins and unravels the release of anions from the protein surface upon protein–DNA association. Furthermore, our solvent paramagnetic relaxation enhancement (PRE) data show how anions are spatially distributed around the protein surface and how their distribution changes when the protein binds to DNA. Our study sheds light on the dynamic behavior of counterions around proteins.  相似文献   
2.
目的 基于超高效液相色谱-四极杆-静电场轨道阱高分辨质谱(UPLC-Q-Exactive-MS)技术对菲牛蛭酶解物中肽段进行鉴定与表征。方法 采用胰蛋白酶对菲牛蛭进行酶解,利用UPLC-Q-Exactive-MS技术结合Maxquant软件对菲牛蛭酶解物进行分析并对其肽段进行序列鉴定,同时采用生物信息学平台对这些肽段进行生物活性与不良反应预测以及相对分子质量、等电点(pI)、净电荷、亲水性氨基酸比例、不稳定指数等基本分子特性的预测。结果 利用UPLC-Q-Exactive-MS技术联合Maxquant软件在菲牛蛭酶解物中共鉴定出32条肽段,其中肽段AGFAGDDAPR的各项肽段分子特性符合目前已知抗血栓肽的共性特征,鉴定分数为103.83,可信度高;活性概率为0.56,相对分子质量976.01,肽链长度为10;平均亲水性为0.5,亲水性氨基酸残基比例为30%,水溶性良好;pI值为4.21,净电荷为-1;不稳定性指数为20.72,在水中稳定性强;具有抗血栓活性的可能性较大。同时6条肽段SSGETSSIIRR、AGFAGDDAPR、SSGETSSIIR、DSYVGDEAQSKR、GARRER、SIEDQVKR被预测具有抗血管生成活性且无溶血现象,但仍需进一步的合成与活性验证。结论 以菲牛蛭为例,提供了一种快速从酶解物中鉴定动物药肽段序列的方法,以期为动物药的肽类成分的研究提供思路。  相似文献   
3.
Rationale:Free-floating thrombi in the intracranial artery are rare. We report a case of a free-floating and spinning thrombus caused by turbulent flow distal to the basilar artery stenosis. We compare thrombus changes in a series of images according to time and describe the approach to treatment and thrombosis resolution.</abstract>Patient concerns:A 55-year-old man presented to the emergency department on March 21, 2020, with left-sided weakness, bilateral limb ataxia, and a one-day history of dysarthria. Brain magnetic resonance imaging showed multifocal infarctions in the pons and cerebellum with severe basilar stenosis.Diagnoses:Digital subtraction angiography showed severe focal stenosis. A relatively large oval-shaped mobile thrombus was observed spinning due to turbulent flow at the distal portion of the stenosis.Interventions:We administered a combination antithrombotic regimen of warfarin and clopidogrel for 50 days.Outcomes:No thrombus was observed on the third follow-up digital subtraction angiography.Lessons:No previous study has directly observed a mobile thrombus in the intracranial artery using digital subtraction angiography. We used a combination antithrombotic strategy, which was effective after long-term, rather than short-term, use.  相似文献   
4.
The growing popularity of solution blow spinning as a method for the production of fibrous tissue engineering scaffolds and the vast range of polymer–solvent systems available for the method raises the need to study the effect of processing conditions on fiber morphology and develop a method for its qualitative assessment. Rheological approaches to determine polymer solution spinnability and image analysis approaches to describe fiber diameter and alignment have been previously proposed, although in a separate manner and mostly for the widely known, well-researched electrospinning method. In this study, a series of methods is presented to determine the processing conditions for the development of submicron fibrous scaffolds. Rheological methods are completed with extensive image analysis to determine the spinnability window for a polymer–solvent system and qualitatively establish the influence of polymer solution concentration and collector rotational speed on fiber morphology, diameter, and alignment. Process parameter selection for a tissue engineering scaffold target application is discussed, considering the varying structural properties of the native extracellular matrix of the tissue of interest.  相似文献   
5.
Potential use of liposome for polycationic colistin is hindered by their phospholipid membrane permeability. In this study, liposomes were modified with sodium cholesteryl sulphate (Chol-SO4?) for improving the colistin loading by enhancing the colistin-bilayer electrostatic attraction. We have evaluated two liposomes: colistin-entrapped liposome of Chol-SO4? (CCL) and coated Chol-SO4?/colistin complex liposome (CCCL). In comparison with CCL which formed large aggregates at Chol-SO4?/colistin charge ratio below 2:1, CCCL showed a smaller size less dependent on the charge ratio, probably arising from more colistin entrapped on the inner leaflet of bilayer. Both liposomes exhibited significantly increased entrapment efficiency as compared with the liposome without Chol-SO4?. But colistin released upon dilution, implying free transfer of colistin through bilayers. Pharmacokinetics results showed the approximately four-fold increase in the plasma AUC0–8?h for CCCL and CCL as compared with colistin solution, showing potential benefit for infectious target localisation by prolonging the systemic circulation of colistin.  相似文献   
6.
《Vaccine》2016,34(34):4032-4039
Development of acellular pertussis vaccine (aPV) requires purification of several components from Bordetella pertussis. While the components pertussis toxin (PT) and filamentous hemagglutinin (FHA) have been successfully purified, the third component, pertactin, proves to be a difficult target due to its very low concentration. In order to solve its purification problem, we performed the surface potential analysis with GRASP2 program. The results demonstrated that there are two major charge patches, one negative and one positive, which are located separately on this linear protein. For this special feature, we designed a dual ion exchange chromatography strategy including an anionic exchange and a cationic exchange process for separation of pertactin from the heat extract of B. pertussis. The initial anionic exchange chromatography concentrated the product from 1.7% to 14.6%, with recovery of 80%. The second cationic exchange chromatography increased the purity to 33%, with recovery of 83%. The final purification was accomplished by hydrophobic interaction chromatography, yielding a purity of 96%. The total recovery of the three columns was 61%. Characterization of the purified antigen was performed with CD, intrinsic fluorescence, HP-SEC and western-blot, showing that the purified protein kept its natural conformation and immune-reactivity. The rationally designed process proved to be feasible, and it is suitable for large-scale preparation of the third aPV component pertactin.  相似文献   
7.
Components:In order to formulate a successful SMEDDS for maximum therapeutic effect, due consideration must be given to various factors such as physicochemical properties of the active moiety as well as excipients, potential for drug excipient interaction (in vitro and in vivo) and physiological factors that promote or inhibit the bioavailability. Further, other important factors such as regulatory status, solubilization capacity, miscibility, physical state of the excipients at room temperature, digestibility and compatibility with capsule shell, chemical stability and cost of the materials should also be considered during the formulation[15]. Such a rationale approach not only helps in reducing the time involved in the formulation development but also reduces the cost of its development[11].

Oil/lipid phase:

The function of oil phase in self-microemulsifying system is to solubilize the hydrophobic/lipophilic active moiety in order to improve both drug loading and bioavailability of the hydrophobic active moiety. Selection of oil plays a vital role in the formulation as it determines the amount of drug that can be solubilized in the system[16]. A lipid molecule with a large hydrophobic portion compared to hydrophilic portion is desirable as it maximizes the amount of drug that can be solubilized. Table 1 represents the most commonly used oils in the formulation of SMEDDS.

TABLE 1

Open in a separate windowLIST OF OILS USED IN FORMULATION OF SMEDDS

Long chain triglycerides:

Lipids that have fatty acid chains of 14-20 carbons are categorized as LCTs[17]. Fixed oils i.e., vegetable oils contain a mixture of glyceride esters of unsaturated long chain fatty acids. These are considered safe as they are commonly present in daily food and are easily digestible[15]. Large hydrophobic portion of triglycerides is responsible for their high solvent capacity for lipophilic moieties. Though it is difficult to microemulsify, some marketed formulations such as Neoral® (composed of olive oil which, has shown superior oral bioavailability) and Topicaine® gel (composed of Jojoba oil for transdermal application) have been successfully practicing the microemulsification of LCTs[18].

Medium chain triglycerides and related esters:

Lipids that have fatty acid chains of 6-12 carbons are categorized as MCTs[17]. MCTs are the most common choice of oil for SMEDDS as they are resistant to oxidation and possess high solvent capacity compared to LCT because of their high effective concentration of ester group. MCTs produced from the distillation of coconut oil are known as glyceryl tricaprylate and comprises of saturated C8 and C10 fatty acids in the liquid state[15]. Labrafac CM 10, a MCT, has shown superior solubility for fenofibrate and produced wider microemulsion region at all surfactant/co-surfactant combinations than Maisine 35, which, is a LCT[19]. Drug substance should possess minimum solubility of 50 mg/ml in LCTs for lymphatic absorption[20]. Upon digestion, products of short and medium chain triglycerides are directed towards portal vein whereas chylomicrons formed from LCTs triggers the lymphatic transport. Further, highly hydrophobic drug substances are easily soluble in vegetable oils and can easily be formulated as simple oil solutions which are readily emulsified in the gut. However, most conventional hydrophobic drug substances do not exhibit superior solubility in LCT such as vegetable oil[21,22].Moderately hydrophobic drug substances, on the other hand, cannot be formulated into simple oil solutions as their solubility is limited. In such cases, SMEDDS are promising alternative where the drug solubility in the oil will be enhanced due to microemulsification of oil by surfactants. It is well accepted that oils with long hydrocarbon chains (high molecular volume) such as soybean oil, castor oil are difficult to microemulsify compared to MCT (low molecular volume) such as capmul MCM and Miglyol. However, solubilizing capacity of oil for lipophilic moiety increases with chain length (hydrophobic portion) of the oil. Hence the selection of oil is a compromise between the solubilizing potential and ability to facilitate the formation of microemulsion[23]. Malcolmson et al. studied the solubility of testosterone propionate in various oils for the formulation of O/W microemulsion and concluded that oils with larger molecular volume such as triglycerides show superior solubility than the corresponding micellar solution containing only surfactants without oil[24,25]. Enhancement of drug solubility in SMEDDS not only relies on the solubility of the drug in the oil but also on the surfactant(s). For instance, ethyl butyrate, small molecular volume oil, has shown higher solubility for testosterone propionate but its ME formulation has only improved the solubility slightly than the corresponding micellar solution. On the contrary, Miglyol 812 which is a larger molecular volume oil has shown improved solubilization in the ME formulation though the solubility of testosterone propionate is less in the individual components compared to ethyl butyrate[24].

Drug solubility in lipid:

Oil component alters the solubility of the drug in SMEDDS by penetrating into the hydrophobic portion of the surfactant monolayer. Extent of oil penetration varies and depends on the molecular volume, polarity, size and shape of the oil molecule. Overall drug solubility in SMEDDS is always higher than the solubility of drug in individual excipients that combine to form SMEDDS. However, such higher solubility considerably depends on the solubility of drug in oil phase, interfacial locus of the drug and drug-surfactant interactions at the interface[26]. In light scattering experiments, it was observed that oils with small molecular volume act like co-surfactants and penetrate into the surfactant monolayer. This forms thinner polyoxyethylene chains near the hydrophobic core of the micelle disrupting the main locus of the drug solubilization due to which, a higher solubility of drug is not observed. Large molecular volume oils, however, forms a distinct core and do not penetrate effectively into the surfactant monolayer. The locus of drug solubilization was found to be effected by the microstructure and solubility of the drug in the excipients. The locus of drug solubilization was found to be at the interface of micelle for phytosterols whereas the same for cholesterol was found to be between the hydrophobic head groups of surfactant molecules. This is attributed to altered side chain flexibility of phytosterol due to the additional substitution of alkyl side chain compared to cholesterol[27].In addition to molecular volume and polarity of the oil, drug solubility in oil is affected by physicochemical properties of drug molecule itself. Consideration of BCS classification and Lipinski''s rule of 5 for the selection of drug is only useful during initial screening stages. As per BCS classification, some of the acidic drugs are listed in Class II despite having good absorption and disposition as they do not satisfy the requirement of higher solubility at low pH values. Lipinski''s rule of 5, on the other hand, holds good only when the drug is not a substrate for the active transporter[4]. This suggests that aqueous solubility and log P alone are not sufficient to predict the solubility of drug in the oil. This further indicates that the solubility of any two drugs with similar log P would not be the same due to their different physicochemical properties.To demonstrate this, a study was conducted in our laboratory with two antihypertensive drugs having close partition coefficient (log P) values, different aqueous solubility and varying physicochemical properties. Candesartan cilexetil is hydrophobic and has log P value of 7.3, molecular weight 610.66 g/mol with a polar surface area 135.77 whereas, valsartan is slightly soluble in aqueous phase with log P value of 5.3, molecular weight 434.53 g/mol with a polar surface area 103.48 (clogP and polar surface area were calculated using chembiodraw ultra 11.0). Unlike candesartan cilexetil, valsartan exhibits pH dependent solubility[28].If only log P and aqueous solubility of these two drugs are considered, it is only natural to assume that candesartan cilexetil would be highly soluble in lipid phase whereas valsartan would be less soluble. A specific and sensitive HPLC-UV method was developed and validated to measure the super saturation solubility of these two drugs in various oils and the results showed a completely different solubility profiles. Solubility profile of these two drugs in different oil phase is given in fig. 2.Open in a separate windowFig. 2Solubility of active ingredients in various oils. Valsartan, candesartan cilexetil.Although log P and polar surface area of valsartan and candesartan cilexetil are closer, their solubility with triacetin, castor oil and capmul MCM C8 differs significantly. This may be attributed to the hydrogen bonding capacity and electrostatic interaction of both the scaffold with the oils. Nevertheless, valsartan is having aliphatic carboxylic group which is expected to be involved in hydrogen bond interaction with the hydrogen acceptor functionality of the triacetin as well as castor oil. We assume that the branched chain aliphatic ester moiety of triacetin, capmul MCM C8 and castor oil gets involved in the electrostatic repulsion with cilexetil part of candesartan. In case of valsartan, such electrostatic interactions are not possible. Furthermore, aliphatic ester chain of triacetin and castor oil may solvate the lipophilic chain of valsartan more favorably than candesartan in the absence of any electrostatic repulsion (proposed interaction is shown in fig. 3). However, significant difference was not observed with other oils such as olive oil, peanut oil, corn oil, miglyol 810, sunflower oil and soybean oil (data not shown).Open in a separate windowFig. 3Proposed interactions of valsartan and candesartan cilexetil with triacetin.  相似文献   
8.
Host factor protein Cyclophilin A (CypA) regulates HIV-1 viral infectivity through direct interactions with the viral capsid, by an unknown mechanism. CypA can either promote or inhibit viral infection, depending on host cell type and HIV-1 capsid (CA) protein sequence. We have examined the role of conformational dynamics on the nanosecond to millisecond timescale in HIV-1 CA assemblies in the escape from CypA dependence, by magic-angle spinning (MAS) NMR and molecular dynamics (MD). Through the analysis of backbone 1H-15N and 1H-13C dipolar tensors and peak intensities from 3D MAS NMR spectra of wild-type and the A92E and G94D CypA escape mutants, we demonstrate that assembled CA is dynamic, particularly in loop regions. The CypA loop in assembled wild-type CA from two strains exhibits unprecedented mobility on the nanosecond to microsecond timescales, and the experimental NMR dipolar order parameters are in quantitative agreement with those calculated from MD trajectories. Remarkably, the CypA loop dynamics of wild-type CA HXB2 assembly is significantly attenuated upon CypA binding, and the dynamics profiles of the A92E and G94D CypA escape mutants closely resemble that of wild-type CA assembly in complex with CypA. These results suggest that CypA loop dynamics is a determining factor in HIV-1''s escape from CypA dependence.Cyclophilin A (CypA), a peptidyl-prolyl isomerase, is a host factor critical in the regulation of the HIV-1 infection, involving a direct interaction with the capsid (CA) protein (13). The mechanism by which CypA modulates the viral infectivity is complex and poorly understood, being dependent on the CA protein primary sequence and the host cell type (46). For example, it is known that mutations in the CypA-binding loop of the CA protein dramatically reduce virus infectivity (7, 8). The A92E and G94D escape mutants bind CypA with similar affinity to wild-type CA, but exhibit only 10% of the activity of wild-type CA in the presence of CypA, and full infectivity can be restored if CypA is inhibited with cyclosporin A in the host cells (8), as shown schematically in SI Appendix, Fig. S1. Alas, the molecular mechanisms underlying CypA escape remain elusive, despite numerous virological, biochemical, and structural–biological studies.The present study investigates the internal conformational dynamics of a CA protein assembly. Although static structures of HIV-1 proteins and complexes with host factors provide important clues into their assembly architecture and conformational details of the interactions, structures alone are insufficient for understanding molecular mechanisms. It is well known that biological functions can be dynamically regulated, at multiple levels of organization, from internal dynamics of individual protein molecules (9) to entire cells. This dynamic regulation certainly also applies to HIV-1 because numerous dynamic processes are associated with HIV-1 assembly, disassembly, release, and maturation (10, 11). For example, we previously demonstrated that internal conformational dynamics of the CA protein and its structural plasticity determine its ability to assemble into pleiomorphic conical capsids (12, 13) (Fig. 1). We also uncovered that, in the HIV-1 CA-SP1 maturation intermediate, dynamic disorder in the SP1 peptide plays an important role in the final step of virus maturation, permitting condensation of CA into the cores of infectious virions (14).Open in a separate windowFig. 1.(A, Left) All-atom MD-derived model of mature HIV-1 capsid constructed on the basis of cryo-electron tomography (cryo-ET) and solution NMR studies (13). The capsid comprises 216 hexamers (orange) and 12 pentamers (blue) [Protein Data Bank (PDB) ID 3J3Y]. Structural organization of a hexamer of hexamers (HOH) building block is illustrated in the expansion. Color coded are individual hexameric units comprising the HOH building block. (A, Right) The 3D structure of CA monomer [HXB2 sequence polymorph [PDB file 3NTE (42)]. (B) Cosedimentation assay of CA with CypA illustrating the efficiency of cosedimentation for different CA/CypA molar ratios. S, supernatant; P, pellet. (C) Transmission electron microscopy (TEM) images of tubular assemblies of CA and CA/CypA. (C, Upper) CA NL4-3 (Left), CA NL4-3 A92E (Center), and CA NL4-3 G94D (Right). (C, Lower) HXB2 (Left) and CA HXB2/CypA (Right). (D) Expansions around the aliphatic region for 2D NCA and combined R2-driven (CORD) MAS NMR spectra for CA HXB2 (black) and CA HXB2/CypA (orange), illustrating the multiple chemical shift perturbations observed upon formation of the complex. These perturbations are mapped onto the structure of CA monomer (A) and are confined to flexible loops and residue variation sites. The spectra are recorded at 20.0 T and the MAS frequency of 14 kHz. (E) Expansions of glycine regions for 2D NCA MAS NMR spectra for (from left to right): HXB2, HXB2/CypA, NL4-3, NL4-3 A92E, and NL4-3 G94D. Dashed lines indicate the G89 cross-peaks associated with cis- and trans-P90.In this study, we examined the residue-specific mobility of CA protein from HXB2 and NL4-3 sequence polymorphs (SI Appendix, Fig. S2) in tubular assemblies on the nanoseconds to milliseconds timescales. In particular, we compared wild-type and A92E and G94D escape mutants of the NL4-3 strain as well as wild-type HXB2 CA alone and in complex with CypA. As discussed previously (14, 15), tubular assemblies recapitulate the hexameric lattice, the predominant symmetry arrangement of the conical HIV-1 capsid core, illustrated in Fig. 1A. Dipolar tensors and resonance intensities extracted from a series of 2D and 3D homonuclear and heteronuclear magic-angle spinning (MAS) NMR experiments revealed that certain regions in both HXB2 and NL4-3 wild-type CA are unusually dynamic on all timescales. These motions are significantly attenuated upon CypA binding. Most remarkably, the dynamic profiles of the A92E and G94D escape mutants closely resemble that of CA when bound by CypA. To gain further understanding of the sequence-dependent dynamics profiles of CA assemblies, we performed extensive molecular dynamics (MD) simulations. The motionally averaged dipolar tensors extracted from the MD trajectories are in remarkable quantitative agreement with the NMR results. Together, our results suggest that changes in the sequence-dependent conformational dynamics may be a key determinant in the escape mechanism of HIV-1 CA capsid mutants from CypA dependence.  相似文献   
9.
A practical aptaprobe for sulfadimethoxine (SDM) detection was established. Based on the electrostatic reaction, a duplex of aptamer and poly(diallyldimethylammonium chloride) (PDDA) was formed, which prevented the quenching effect of PDDA on the fluorescence of CdTe quantum dots (QDs). But the specifically binding of aptamer to SDM might result in free PDDA released and the fluorescence was quenched. Based on the fluorescence aptaprobe, SDM was quantitatively detected by measuring the fluorescence at 530 nm with a linear range of 25–300 ng mL−1, and the limit of detection was 2.24 ng mL−1 based on 3σ/K (n = 9). The aptaprobe was applied to SDM detection with recoveries of 94.2 %–113 % and 104 %–118 % for seawater and fish, respectively. The results showed that the fluorescence aptaprobe was simple and convenient for the rapid detection of SDM residue in water and fish samples.  相似文献   
10.
目的: 对一种新型聚乳酸-羟基乙酸(polylactic acid-glycolic acid,PLGA)/鱼皮胶原共轭静电纺丝膜的生物相容性进行分析。方法: 以PLGA和医用级鱼皮Ⅰ型胶原为原材料,通过共轭静电纺丝技术制备出高取向性的纳米纤维膜,然后分别以小鼠成纤维细胞L929为研究模型,初步评价其细胞、组织相容性,为其用于种植骨组织再生(guided bone regeneration,GBR)提供实验依据。结果: 纤维细胞在纤维膜表面黏附生长良好,有大量细胞伸出伪足,沿着纤维的取向进行铺展排列。结论: PLGA/鱼皮胶原共轭静电纺丝膜有利于成纤维细胞生长,可望用于种植骨组织再生。  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号