全文获取类型
收费全文 | 1596篇 |
免费 | 64篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 33篇 |
妇产科学 | 12篇 |
基础医学 | 154篇 |
口腔科学 | 29篇 |
临床医学 | 129篇 |
内科学 | 378篇 |
皮肤病学 | 21篇 |
神经病学 | 50篇 |
特种医学 | 15篇 |
外科学 | 210篇 |
综合类 | 50篇 |
一般理论 | 4篇 |
预防医学 | 82篇 |
眼科学 | 42篇 |
药学 | 288篇 |
中国医学 | 38篇 |
肿瘤学 | 128篇 |
出版年
2023年 | 13篇 |
2022年 | 43篇 |
2021年 | 61篇 |
2020年 | 26篇 |
2019年 | 47篇 |
2018年 | 42篇 |
2017年 | 53篇 |
2016年 | 39篇 |
2015年 | 40篇 |
2014年 | 77篇 |
2013年 | 113篇 |
2012年 | 115篇 |
2011年 | 120篇 |
2010年 | 76篇 |
2009年 | 43篇 |
2008年 | 87篇 |
2007年 | 106篇 |
2006年 | 83篇 |
2005年 | 90篇 |
2004年 | 74篇 |
2003年 | 73篇 |
2002年 | 76篇 |
2001年 | 24篇 |
2000年 | 17篇 |
1999年 | 27篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 14篇 |
1995年 | 6篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1962年 | 1篇 |
排序方式: 共有1666条查询结果,搜索用时 47 毫秒
161.
Quality by design (QbD) principles were explored in the current study to gain a comprehensive understanding of the preparation of superoxide dismutase (SOD) containing liposome formulations prepared using freeze-and-thaw unilamellar vesicles (FAT-ULV). Risk analysis and D-optimal statistical design were performed. Of all the variables investigated, lipid concentration, cholesterol mol%, main lipid type and protein concentration were identified as critical parameters affecting SOD encapsulation efficiency, while the main lipid type was the only factor influencing liposome particle size. Using a model generated by the D-optimal design, a series of three-dimensional response spaces for SOD liposome encapsulation efficiency were established. The maximum values observed in the response surfaces indirectly confirmed the existence of a specific SOD-lipid interaction, which took place in the lipid bilayer under the following optimal conditions: (1) appropriate membrane thickness and curvature (DPPC liposomes); and (2) optimal "pocket size" generated by cholesterol content. With respect to storage stability, the prepared SOD liposomes remained stable for at least 6 months in aqueous dispersion state at 4°C. This research highlights the level of understanding that can be accomplished through a well-designed study based on the philosophy of QbD. 相似文献
162.
Zidan AS Rahman Z Sayeed V Raw A Yu L Khan MA 《International journal of pharmaceutics》2012,423(2):341-350
Different destructive and nondestructive analytical methods, namely powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), Raman and near-infrared (NIR) spectroscopy and imaging, to detect and characterize tacrolimus trace crystallinity in an amorphous solid dispersion (SD) using chemometric analysis were developed. The SD was spiked with different percentages of the crystalline drug to construct an array of SDs with different crystallinity percentages. Partial least square (PLS) regression analysis was employed to compare the performance of the calibration models created using these analytical methods. The obtained results indicated a significant interaction between tacrolimus and the employed polymer and a drug dissolution dependency on the crystalline fraction within the SDs. Using two PLS factors, these analytical methods were ranked according to its specificity to detect the trace crystallinity of SDs as NIR > PXRD > Raman > DSC. Through the application of PLS, root-mean-squared error of calibration values of 2.91%, 5.36%, 7.07% and 11.58% were calculated for the calibration models constructed by NIR, PXRD, Raman and DSC, respectively. Having a prediction error of 2.1% and a correlation coefficient of 0.99, it is demonstrated that combined NIR imaging and chemometric analysis outperformed the other methods in detecting trace crystallinity in tacrolimus amorphous systems. The spatial distributions of amorphous and crystalline drug were also obtained in order to allow for studying the crystallization dissemination in the solid dispersions. Consequently, NIR and NIR imaging coupled with chemometry was shown to be a powerful tool for the prediction of drug crystallinity within SDs. 相似文献
163.
Two statistical designs were used in this case study as part of an investigation into the feasibility and the advantages of applying QbD concepts to liposome-based complex parenteral controlled release systems containing a hydrophilic active pharmaceutical ingredient (API). The anti-viral drug Tenofovir was used as a model compound. First design (Plackett-Burman) was used to screen eight high-risk variables obtained from risk analysis and assess their impact on liposome characteristics (drug encapsulation efficiency, particle size, and physical stability). It was discovered that out of eight high-risk variables only lipid and drug concentration had significant effects on the drug encapsulation efficiency. This allowed the use of a central composite design (CCD) (with more predictive capability) to fully elucidate the relationship between lipid concentration, drug concentration and encapsulation efficiency. On comparing the CCD model generated response surface with additional data points, the accuracy and robustness of the model was confirmed. Using this developed model, the design space for Tenofovir liposomes preparation has been established in a laboratory setting, within which the preparation variability is minimized. With regard to sample storage stability, it was shown that at 4 °C the prepared Tenofovir liposomes, dispersed in aqueous phase, achieved stability for at least 2 years. These principles can be applied to liposomes containing other hydrophilic APIs, and can provide time and cost saving to industrial formulation scientists, and result in a more robust liposome preparation process. 相似文献
164.
Tas C Mansoor S Kalluri H Zarnitsyn VG Choi SO Banga AK Prausnitz MR 《International journal of pharmaceutics》2012,423(2):257-263
Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL min). Tmax (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections. 相似文献
165.
The complete sequences of a begomovirus and an associated betasatellite isolated from Croton bonplandianus originating from Pakistan were determined. The sequence of the begomovirus showed the highest level of nucleotide sequence
identity (88.9%) to an isolate of papaya leaf curl virus and thus represents a new species, for which we propose the name
Croton yellow vein virus (CYVV). The sequence of the betasatellite showed the highest levels of sequence identity (82 to 98.4%)
to six sequences in the databases that have yet to be reported, followed by isolates of tomato leaf curl Joydebpur betasatellite
(48.7 to 52.5%). This indicates that the betasatellite identified here (and the six sequences in the databases) is an isolate
of a newly identified species for which the name Croton yellow vein mosaic betasatellite (CroYVMB) is proposed. For the begomovirus,
an analysis of the sequence indicates that it has a recombinant origin. 相似文献
166.
Amin I Ilyas M Qazi J Bashir R Yadav JS Mansoor S Fauquet CM Briddon RW 《Virus genes》2011,42(2):272-281
Five genes encoded by Banana bunchy top virus (BBTV) originating from Pakistan were expressed in Nicotiana benthamiana using a Potato virus X (PVX) vector. Expression of the master replication-associated protein (mRep) and movement protein
(MP) resulted in necrotic cell death of inoculated tissues, as well as leaf curling and necrosis along the veins in newly
emerging leaves. The systemic necrosis induced by the expression of MP was discolored (dark) in comparison to that induced
by mRep. Expression of the cell-cycle link protein (Clink), the coat protein (CP), and the nuclear shuttle protein from the
PVX vector induced somewhat milder symptoms, consisting of mild leaf curling and mosaic, although expression of the CP caused
a necrotic response in inoculated leaf. The accumulation of viral RNA was enhanced by MP, Clink, and CP. Of the five BBTV-encoded
gene products two, the MP and Clink, stabilized GFP-specific mRNA and reduced GFP-specific small interfering RNA in N. benthamiana line 16c when expressed under the control of the 35S promoter and co-inoculated with a construct for the expression of GFP
hairpin RNA construct. These results identified MP and Clink as suppressors of RNA silencing. Taken together the ability of
MP to induce severe symptoms in plants and suppress RNA silencing implicates this product as a major pathogenicity determinant
of BBTV. 相似文献
167.
168.
Shyam Singh Mukhand L. Sharma Reyaz A. Lone Mehmood A. Wani Zahur Hussain Ishtiyaq Mir Puja Vimesh 《World journal of surgery》2009,33(3):489-491
Background Hemothorax has been reported to occur along with spontaneous pneumothorax due to adhesion disruption. Rupture of pleural adhesions
spontaneously or after unnoticeable trivial trauma causing massive hemothorax alone is rare.
Methods We present a series of seven cases of idiopathic massive spontaneous hemothorax due to adhesion disruption, of which all required
emergency thoracotomy with ligation or cauterization of bleeding adhesions.
Results Six patients had bleeding pleural lung adhesions of which five involved the upper lobes. Another had bleeding from pleuropericardial
adhesions. All patients are doing well on follow-up.
Conclusions Disruption of pleural adhesions may cause massive hemothorax, requiring early surgical intervention. After thoracotomy the
outcome in these patients is excellent. 相似文献
169.
Bokhari A Nizamani NM Jackson DJ Rehan NE Rahman M Muzaffar R Mansoor S Raza H Qayum K Girault P Pisani E Thaver I 《International journal of STD & AIDS》2007,18(7):486-492
The objective of this study was to measure HIV prevalence and risk behaviour in injecting drug users (IDUs), male sex workers (MSWs), Hijras (transgenders), female sex workers (FSWs) and male truckers in Karachi and Lahore, Pakistan. The design was a linked-anonymous cross-sectional study of individuals identified at key venues or through peer referral. Approximately 400 respondents in each group (200 for Hijras) responded to a standardized questionnaire and were tested for HIV antibodies at each site. In Karachi, 23% of IDUs and 4% of MSWs were HIV positive, and HIV-positive individuals were identified in all risk groups in at least one city. Two-thirds of all IDUs used a shared needle in the previous week, and unprotected commercial sex activity with men and women was high. The HIV epidemic has entered IDU and male and female commercial sex networks in Karachi and Lahore. Targeted intervention services must be scaled up and risk group surveillance intensified. 相似文献
170.
Laura Caruso Stella Yuen Julie Smith Mansoor Husain Mary Anne Opavsky 《Journal of molecular and cellular cardiology》2010,48(6):1194-1205
The coxsackie–adenovirus receptor (CAR) is an adhesion molecule found at the intercalated disc of cardiomyocytes in association with other adherens and tight junction proteins. CAR expression is increased at cardiomyocyte junctions in patients with heart failure. It is not known what contribution elevated CAR expression makes to cardiac pathology. We generated a binary transgenic mouse enabling cardiac-restricted doxycycline-regulated expression of Flag-tagged murine CAR (mCAR+/αMtTA+ mice). Myocardial CAR levels were increased 6-fold in mCAR+/αMtTA+ mice, localizing to intercalated discs and sarcolemma. Well at birth, mCAR+/αMtTA+ mice developed a severe cardiomyopathy and died by 4 weeks. Cardiomyocyte hypertrophy was evident at 1 week, with increased heart:body weight ratios by 3 weeks. Disorganization and degeneration of cardiomyocytes were evident with disrupted adherens junctions. Doxycycline administration turned off transgene expression and rescued mice from the development of the cardiomyopathic phenotype. In CAR-overexpressing mCAR+/αMtTA+ mice, adherens junction proteins were abnormally expressed. N-cadherin protein levels were 83% lower in mCAR+/αMtTA+ hearts vs controls at 1 week, with levels subsequently increased above controls at 3 weeks. β-catenin expression was 90% and 135% above controls at 1 and 3 weeks, respectively. Nuclear translocation of β-catenin in cardiomyocytes of mCAR+/αMtTA+ mice was associated with increased c-myc RNA, a target of active β-catenin known to be associated with cardiac hypertrophy. Our study is the first to demonstrate that increased CAR expression can induce a cardiomyopathy and supports a model whereby the pathogenesis is determined by CAR stimulated β-catenin signaling, and/or disruption of the adherens junction. 相似文献