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1.
羟基红花黄色素A对血小板活化因子的拮抗作用   总被引:64,自引:0,他引:64  
臧宝霞  金鸣  司南  张彦  吴伟  朴永哲 《药学学报》2002,37(9):696-699
目的观察羟基红花黄色素A(HSYA)对血小板活化因子(PAF)的拮抗作用.方法以放射受体结合试验观察HSYA抑制[3H]PAF与家兔洗涤血小板(WRP)特异性结合的作用,以比浊法观察HSYA抑制PAF介导的WRP及兔多型核白细胞(PMNs)聚集的作用.结果 HSYA可浓度依赖地抑制1,2及4 nmol·L-1 [3H]PAF与WRP受体的结合;HSYA抑制PAF介导的WRP及兔PMNs聚集,均具明显的量效关系,其IC50分别为0.99及0.70 mmol·L-1.结论 HSYA有PAF受体拮抗作用.  相似文献
2.
Amyloid beta protein (Abeta)- and human group IIA secretory phospholipase A(2) (sPLA(2)-IIA)-induced neuronal cell death have been established as in vitro models for Alzheimer's disease (AD) and stroke. Both sPLA(2)-IIA and Abeta causes neuronal apoptosis by increasing the influx of Ca(2+) through L-type voltage-sensitive Ca(2+) channel (L-VSCC). In the present study, we evaluated effects of a selective L-VSCC blocker, S-(+)-methyl 4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitro-phenyl)thieno[2,3-b]pyridine-5-carboxylate (S-312-d), on Abeta- and sPLA(2)-IIA-induced neuronal apoptosis in primary cultures of rat cortical neurons. S-312-d significantly rescued cortical neurons from Abeta- and sPLA(2)-IIA-induced cell death. Both cell death stimuli caused the appearance of apoptotic features such as plasma membrane blebs, chromatin condensation, and DNA fragmentation. S-312-d completely suppressed these apoptotic features. Before apoptosis, the two death ligands markedly enhanced an influx of Ca(2+) into neurons. S-312-d significantly prevented neurons from sPLA(2)-IIA- and Abeta-induced Ca(2+) influx. Furthermore, the neuroprotective effect of S-312-d was more potent than that of another L-VSCC blocker, nimodipine. On the other hand, blockers of other VSCCs such as the N-type and P/Q-type calcium channels had no effect on the neuronal cell death, apoptotic features and Ca(2+) influx. In conclusion, we demonstrated that S-312-d rescues cortical neurons from Abeta- and sPLA(2)-IIA-induced apoptosis.  相似文献
3.
多肽、蛋白质药物的聚乳酸及其共聚物微球研究进展   总被引:14,自引:0,他引:14  
综述了以可生物降解的合成高分子材料-聚乳酸及其共聚物为载体的多肽,蛋白质药物微球的制备方法和影响因素。讨论了蛋白质在制备和释放过程中的稳定性。  相似文献
4.
盐酸多西环素注入用缓释凝胶的体外释放度研究   总被引:13,自引:1,他引:12  
目的:考察盐酸多西环素注入用缓释凝胶的体外释放特性及机制;方法:考察聚乳酸(PLA)和聚乳酸-羟基乙酸共聚物(PLGA)型号、聚合物浓度、含药量、释放介质和释放装置对药物释放的影响,制定出盐酸多西环素注入用缓释凝胶的体外释放试验方案并进行体外释放度测定;结果:凝胶中药物在水中的释放分为2个阶段:第1个阶段为“突释”,第2个阶段符合Higuichi方程。结论:所定方法可用于盐酸多西环素注入用缓释凝胶的体外释放试验。  相似文献
5.
Controlled DNA Delivery Systems   总被引:11,自引:0,他引:11  
Purpose. Genes are of increasing interest as pharmaceuticals, but current methods for long-term gene delivery are inadequate. Controlled release systems using biocompatible and/or biodegradable polymers offer many advantages over conventional gene delivery approaches. We have characterized systems for controlled delivery of DNA from implantable polymer matrices (EVAc: poly (ethylene-co-vinyl acetate)) and injectable microspheres (PLGA and PLA: poly (D, L-lactide-co-glycolide) copolymer and poly (L-lactide), respectively). Methods. Herring sperm DNA and bacteria phage DNA were encapsulated as a model system. Released DNA concentration was determined by fluoroassays. Agarose electrophoresis was used to determine the dependence of release rate on DNA size. The Green Fluorescent Protein (GFP) gene was used to determine the integrity and functionality of released DNA. Results. Both small and large DNA molecules (herring sperm DNA, 0.1–0.6 kb; GFP, 1.9 kb; DNA, 48.5 kb) were successfully encapsulated and released from EVAc matrices, and PLGA or PLA microspheres. The release from DNA-EVAc systems was diffusion-controlled. When co-encapsulated in the same matrix, the larger DNA was released more slowly than herring sperm; the rate of release scaled with the DNA diffusion coefficient in water. The chemical and biological integrity of released DNA was not changed. Conclusions. These low cost, and adjustable, controlled DNA delivery systems, using FDA-approved biocompatible/biodegradable and implantable/injectable materials, could be useful for in vivo gene delivery, such as DNA vaccination and gene therapy.  相似文献
6.
目的:对近年来以PLA,PLGA为载体的微球剂的研究进展进行综述。方法:查阅近10年来有关PLA,PLGA微球研究的国内外文献,介绍此类微球的制备方法和影响其体外释放等性质的主要因素。结果:PLA,PLGA的性质,药和折性质及微球的制备工艺等对微球的体外释放等性质均有重要的影响。结论:对以PLA,PLGA为载体制备的药物微球,有待于更进一步的研究和开发。  相似文献
7.
异烟肼肺靶向性微球的制备及其小鼠体内分布   总被引:9,自引:1,他引:8  
目的:制备异烟肼肺靶向性微球,评价其体外释药特性及在动物体内的肺靶向性。方法:采用溶剂挥发法制备微球,动态透析法考察其体外释药性能,实验动物静脉注射后测定其各组织的药物浓度,研究其体内相对分布百分率及肺靶向性。结果:制得的微球粒径在7~30μm的占微球总数的88.8%,平均粒径为(16.7±4.6)μm,包封率为86.92%,载药量为(40.7±3.6)%(n=5),体外释药T50为68min,轻对照组延长了4.5倍。动物实验表明,制得微球后,药物在肺内的相对分布百分率明显高于其它组织与血液,并轻对照组提高了4倍。结论:本法制得的异烟肼微球具有明显的缓释性及肺靶向性。  相似文献
8.
喷雾干燥技术在蛋白、多肽类药物微球制备中的应用   总被引:8,自引:0,他引:8  
白洁  何应 《药学进展》2007,31(7):298-302
按照不同的常用载体材料(聚乳酸类和壳聚糖类),分类综述应用喷雾干燥技术制备蛋白、多肽类药物微球的研究进展,主要介绍和比较了溶液,喷雾干燥、乳剂,喷雾干燥、喷雾冷冻干燥、喷雾液中冷冻及低温喷雾提取等制备工艺的特点。  相似文献
9.
We have demonstrated that magnolol suppressed thromboxane B2 (TXB2) and leukotriene B4 (LTB4) formation in A23187-stimulated rat neutrophils. Maximum inhibition was obtained with about 10 microM magnolol. Magnolol was more effective in the inhibition of cyclooxygenase (COX) activity than in the inhibition of 5-lipoxygenase (5-LO) activity as assessed by means of enzyme activity determination in vitro and COX and 5-LO metabolic capacity analyses in vivo. Magnolol alone stimulated cytosolic phospholipase A2 (cPLA2) phosphorylation and the translocation of 5-LO and cPLA2 to the membrane, and evoked arachidonic acid (AA) release. Recruitment of both 5-LO and cPLA2 to the membranes was suppressed by EGTA. Arachidonyl trifluoromethyl ketone (AACOCF3), a PLA2 inhibitor, bromoenol lactone (BEL), a Ca2+-independent PLA2 (iPLA2) inhibitor, and EGTA suppressed the magnolol-induced AA release. However, none of the follows affected magnolol-induced AA-release: 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580), a p38 mitogen-activated protein kinase (MAPK) inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), a MAPK kinase (MEK) inhibitor, or 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide (GF109203X), a protein kinase C (PKC) inhibitor. In addition, magnolol at 30 microM did not stimulate the p38 MAPK and extracellular signal-regulated kinase 2 (ERK2) enzyme activities. These results indicated that magnolol inhibits the formation of prostaglandins and leukotrienes in A23187-stimulated rat neutrophils, probably through a direct blockade of COX and 5-LO activities. The stimulatory effects of magnolol at high concentration on the membrane association of 5-LO and cPLA2 are attributable to the elevation of [Ca2+]i, and on the AA release is likely via activation of cPLA2 and iPLA2.  相似文献
10.
PLA-PEG嵌段共聚物在药物释放系统中的应用   总被引:6,自引:0,他引:6  
虞阳  涂家生  张明  李朋梅 《药学进展》2005,29(6):250-254
介绍PLA-PEG嵌段共聚物的合成和性质,综述其作为胶束、微球、纳米粒等的载体在药物释放系统中的应用。聚乳酸-聚乙二醇嵌段共聚物因具备良好的生物可降解性和相容性而得到广泛应用。  相似文献
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