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61.
62.
Novel pH-sensitive hydrogel beads were prepared using a hydrolyzed poly(acrylamide-g-xanthan) (PAAm-g-XG) copolymer from a complete aqueous environment and evaluated for targeting ketoprofen to the intestine. The PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The copolymer was characterized by FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis and thermogravimetric analysis. Pulsatile swelling study indicated that the copolymer exhibits considerable pH-sensitive behavior unlike pristine xanthan gum. Ketoprofen-loaded pH-sensitive beads were prepared by ionotropic gelation with Al3 + ions. Release of drug from all the copolymeric beads was much lesser than that from pristine xanthan beads. Moreover, a maximum of 20% ketoprofen was released from the copolymeric beads in pH 1.2–5.5 during a period of 3 h, while a major portion of the drug was released in pH 6.8–7.4 gradually over a longer period. Pharmacodynamic activity and stomach histopathology of albino rats indicated that the beads were able to retard the drug release in stomach, and gastric side effects such as ulceration, hemorrhage and erosion of gastric mucosa were diminished when the drug was entrapped into PAAm-g-XG-based pH-sensitive beads. 相似文献
63.
Abdallah Makhlof Yuichi Tozuka Hirofumi Takeuchi 《European journal of pharmaceutical sciences》2011,42(5):2329-451
Chitosan nanoparticles (CS NPs) have been commonly regarded as potential carriers for the mucosal delivery of therapeutic peptides because of their biocompatibility, bioadhesion and permeation enhancing properties. However, they have limited colloidal stability and readily dissociate and dissolve in the acidic gastric conditions. In the current study, CS NPs were formulated by ionic cross-linking with hydroxypropyl methylcellulose phthalate (HPMCP) as a pH-sensitive polymer and evaluated for the oral delivery of insulin. In vitro results revealed a superior acid stability of CS/HPMCP NPs with a significant control over insulin release and degradation in simulated acidic conditions with or without pepsin. Furthermore, fluorescently-labeled CS/HPMCP NPs showed a 2- to 4-fold improvement in the intestinal mucoadhesion and penetration compared to CS/TPP NPs as evidenced by quantitative fluorescence analysis and confocal microscopy. After s.c. injection to rats, no significant difference in the hypoglycemic effect of insulin solution or insulin-loaded CS/HPMCP NPs was observed, confirming the physico-chemical stability and biological activity of the entrapped peptide. Following peroral administration, CS/HPMCP NPs increased the hypoglycemic effect of insulin by more than 9.8 and 2.8-folds as compared to oral insulin solution and insulin-loaded CS/tripolyphosphate (TPP) NPs, respectively. 相似文献
64.
The present review provides an overview on the recent progress in the development of pH- and sugar-sensitive layer-by-layer (LbL) thin films and microcapsules in relation to their potential applications in drug delivery. pH-sensitive LbL films and microcapsules have been studied for the development of peptide and protein drug delivery systems to the gastrointestinal tract, anti-cancer drugs to tumor cells, anti-inflammatory drugs to inflamed tissues, and the intracellular delivery of DNA, where pH is shifted from neutral to acidic. pH-induced decomposition or permeability changes of LbL films and microcapsules form the basis for the pH-sensitive release of drugs. Sugar-sensitive LbL films and microcapsules have been studied mainly for the development of an artificial pancreas that can release insulin in response to the presence of glucose. Therefore, glucose oxidase, lectin, and phenylboronic acid have been used for the construction of glucose-sensitive LbL films and microcapsules. LbL film-coated islet cells are also candidates for an artificial pancreas. An artificial pancreas would make a significant contribution to improving the quality of life of diabetic patients by replacing repeated subcutaneous insulin injections. 相似文献
65.
目的考察以共聚物瓜耳胶-g-丙烯酰胺-丙烯酸(GPAA)为辅料,酮洛芬(KP)为模型药物的控释片释药特征。方法考察可溶性添加剂、释放介质pH及离子强度、GPAA用量、GPAA组成对GPAA控释片中药物的释放。结果凝胶中KP在0.1mol·L^-1HCl中,2h累积释放量〈10%,在pH6.8PBS中12h累积释放超过90%;凝胶中KP释放随释放介质离子强度增加而减慢;随可溶性成分含量增加而加快,随GPAA含量的增加而减慢;随着GPAA中丙烯酸(AAc)所占比例增加,KP在pH6.8PBS释放速度减小,在0.1mol·L^-1HCl中释放速率无明显变化。结论以GPAA为骨架材料的控释片释药具有明显的pH敏感性。 相似文献
66.
目的 研究左乙拉西坦(LEV)pH敏感鼻用凝胶在大鼠体内的药代动力学.方法 用高效液相色谱法测定大鼠血中LEV的浓度.色谱柱为Wondasil C18柱(250.0 mm×4.6 mm,5.0μm),流动相为乙腈-水(11:89),检测波长为205 nm,内标为甲硝唑.按照体质量将大鼠随机分为实验组和对照组,每组6只.... 相似文献
67.
Pharmaceutical Research - 相似文献
68.
Delivery of Plasmid DNA into Mammalian Cell Lines Using pH-Sensitive Liposomes: Comparison with Cationic Liposomes 总被引:9,自引:0,他引:9
We compare the transfection efficiency of plasmid DNA encoding either luciferase or (-galactosidase encapsulated in pH-sensitive liposomes or non-pH-sensitive liposomes or DNA complexed with cationic liposomes composed of dioleoyloxypropyl-trimethylammonium:dioleoylphosphatidyl-ethanolamine (1:1, w/w) (Lipofectin) and delivered into various mammalian cell lines. Cationic liposomes mediate the highest transient transfection level in all cell-lines examined. pH-sensitive liposomes, composed of cholestryl hemisuccinate and dioleoylphosphatidylethanolamine at a 2:1 molar ratio, mediate gene transfer with efficiencies that are 1 to 30% of that obtained with cationic liposomes, while non-pH-sensitive liposome compositions do not induce any detectable transfection. Cationic liposomes mediate a more rapid uptake of plasmid DNA, to about an eightfold greater level than that obtained with pH-sensitive liposomes. The higher uptake of DNA mediated by Lipofectin accounts for part of its high transfection efficiency. Treatment of cells with chloroquine, ammonium chloride, or monensin decreases (threefold) transfection using pH-sensitive liposomes and either has no effect on or enhances cationic liposome-mediated transfection. Therefore plasma membrane fusion is not the only mechanism available to cationic liposomes; in certain cell lines DNA delivery via endocytosis is a possible parallel pathway and could augment the superior transfection efficiency observed with cationic liposomes. 相似文献
69.
Mojaverian Parviz Reynolds James C. Ouyang Ann Wirth Fern Kellner Paul E. Vlasses Peter H. 《Pharmaceutical research》1991,8(1):97-100
We studied the mechanism of gastric emptying of a pH-sensitive radiotelemetry capsule with respect to phases of the interdigestive migrating motor complex (IMMC) in fasting normal volunteers and the effect of the Heidelberg capsule (HC) on the duration or timing of the IMMC phases. A manometric catheter with eight mounted solid-state strain gauges was passed transnasally and positioned fluoroscopically in the duodenum and jejunum in four normal, fasted male volunteers, in their right lateral position. The HC was administered orally following the establishment of one complete IMMC cycle (defined by the recording time between the end of two subsequent phase III activity fronts) and during the beginning of Phase I of the next cycle. The gastric residence time (GRT) of the HC was measured as the time of a gastric pH rise of 3.0 units. In three subjects, GRT of the HC lasted to within 5 min of the onset of the next duodenal phase III of the IMMC, while in the fourth subject, the HC passed during the second phase III activity front. There were no significant differences in the duration of each phase of duodenal IMMC in the presence or absence of the HC (Phase I, 54 ± 9.3 vs 31.6 ± 10.1; Phase II, 22 ± 8.1 vs 58.9 ± 32; Phase III, 5.3 ± 0.7 vs 4.2 ± 0.7 min; mean ± SE; P > 0.1 in all phases). In addition, the HC had no effect on motility index or patterns of contractions. The Heidelberg radiotelemetry device (7 × 20 mm) may be used as a noninvasive, nonradioactive means of measuring the activity of the IMMC and the presence of Phase III peak IMMC activity. Further, it permits detailed evaluation of the emptying patterns of solid dosage forms (i.e., enteric-coated tablet or controlled-release matrix) in humans under fasted or fed conditions. 相似文献
70.
《Expert opinion on drug delivery》2013,10(3):307-319
Importance of the field: Dendrimers are synthetic macromolecules with well-defined structures, many terminal functional groups, and an inner space to hold small molecules. These properties make them potential drug carriers. Recently, stimuli-responsive drug delivery systems have become attractive because of the reduction of side effects and maximum expression of drug action.Areas covered in this review: This paper reviews dendrimer nanoparticles that are sensitive to temperature, light, pH and redox state.What the reader will gain: Strategies to design these dendritic polymers are provided in this review.Take home message: By adding stimuli-responsive properties to the dendrimers, dendritic polymers capable of controlled release can be produced. These stimuli-responsive dendrimers are a potential next generation drug carrier. 相似文献