全文获取类型
收费全文 | 6397篇 |
免费 | 430篇 |
国内免费 | 8篇 |
专业分类
6835篇 |
出版年
2023年 | 54篇 |
2022年 | 157篇 |
2021年 | 280篇 |
2020年 | 124篇 |
2019年 | 157篇 |
2018年 | 204篇 |
2017年 | 155篇 |
2016年 | 184篇 |
2015年 | 307篇 |
2014年 | 338篇 |
2013年 | 475篇 |
2012年 | 472篇 |
2011年 | 414篇 |
2010年 | 235篇 |
2009年 | 207篇 |
2008年 | 249篇 |
2007年 | 263篇 |
2006年 | 228篇 |
2005年 | 197篇 |
2004年 | 202篇 |
2003年 | 162篇 |
2002年 | 166篇 |
2001年 | 124篇 |
2000年 | 108篇 |
1999年 | 82篇 |
1998年 | 44篇 |
1997年 | 40篇 |
1996年 | 39篇 |
1995年 | 28篇 |
1994年 | 26篇 |
1992年 | 63篇 |
1991年 | 74篇 |
1990年 | 74篇 |
1989年 | 61篇 |
1988年 | 68篇 |
1987年 | 49篇 |
1986年 | 41篇 |
1985年 | 55篇 |
1984年 | 49篇 |
1983年 | 43篇 |
1982年 | 26篇 |
1980年 | 32篇 |
1979年 | 39篇 |
1978年 | 43篇 |
1977年 | 33篇 |
1976年 | 34篇 |
1974年 | 40篇 |
1973年 | 27篇 |
1971年 | 25篇 |
1970年 | 27篇 |
排序方式: 共有6835条查询结果,搜索用时 11 毫秒
201.
Oxidative damage to the vascular endothelial cells may play a crucial role in mediating glucose-induced cellular dysfunction in chronic diabetic complications. The present study was aimed at elucidating the role of glucose-induced alteration of highly inducible heme oxygenase (HO) in mediating oxidative stress in the vascular endothelial cells. We have also investigated the interaction between HO and the nitric oxide (NO) system, and its possible role in alteration of other vasoactive factors.Human umbilical vein endothelial cells (HUVECs) were exposed to low (5?mmol/l) and high (25?mmol/l) glucose levels. In order to determine the role of HO in endothelial dysfunction and to elucidate a possible interaction between the HO and NO systems, cells were exposed to HO inducer (hemin, 10?μmol/l), HO antagonist (SnPPIX, 10?μmol/l), and NO synthase blocker (l-NAME, 200?μmol/l) with or without NO donor (arginine, 1?mmol/l). mRNA expression of HO and NO isoforms was measured by real time RT-PCR. HO activity was measured by bilirubin production and cellular oxidative stress was assessed by 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nitrotyrosine staining. We also determined the expression of vasoactive factors, endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF).In the endothelial cells, glucose caused upregulation of HO-1 expression and increased HO activity. A co-stimulatory relationship between HO and NO was observed. Increased HO activity also associated with oxidative DNA and protein damage in the endothelial cells. Furthermore, increased HO activity augmented mRNA expression of vasoactive factors, ET-1 and VEGF. These data suggest that HO by itself and via elaboration of other vasoactive factors may cause endothelial injury and functional alteration. These findings are of importance in the context of chronic diabetic complications. 相似文献
202.
203.
Abhinav Shrivastava M.Sc. Abdul Arif Khan Archana Shrivastav Sudhir K. Jain Pradeep K. Singhal 《Preparative biochemistry & biotechnology》2013,43(6):574-581
L-Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and other related malignancies. Its further use includes reduction of asparagine concentration in food products, which may lead to formation of acrylamide. Currently bacterial asparaginase is produced at industrial scale, but the enzyme isolated from bacterial origin is often associated with adverse reactions. These side effects require development of asparaginase from alternative sources. In the present study, Penicillium digitatum was explored for the production of extracellular L-asparaginase using modified Czapek–Dox media. The enzyme was purified about 60.95-fold and then kinetic study showed that the Km value of the enzyme was 1 × 10?5 M. The optimum pH and temperature for the enzyme were 7.0 and 30°C, respectively. The optimum incubation period for L-asparaginase was 15 min. This work concludes that this enzyme can be a suitable candidate due to its strong kinetic properties, and further research can usher into development of asparaginase formulation from fungal origin with less adverse effects. 相似文献
204.
Muhammad Yasir Haji Khan Syed Sikander Azam Amar Telke Seon Won Kim Young Ryun Chung 《Journal of microbiology (Seoul, Korea)》2013,51(3):329-335
In the vermicomposting of paper mill sludge, the activity of earthworms is very dependent on dietetic polysaccharides including cellulose as energy sources. Most of these polymers are degraded by the host microbiota and considered potentially important source for cellulolytic enzymes. In the present study, a metagenomic library was constructed from vermicompost (VC) prepared with paper mill sludge and dairy sludge (fresh sludge, FS) and functionally screened for cellulolytic activities. Eighteen cellulase expressing clones were isolated from about 89,000 fosmid clones libraries. A short fragment library was constructed from the most active positive clone (cMGL504) and one open reading frame (ORF) of 1,092 bp encoding an endo-β-1,4-glucanase was indentified which showed 88% similarity with Cellvibrio mixtus cellulase A gene. The endo-β-1,4-glucanase cmgl504 gene was overexpressed in Escherichia coli. The purified recombinant cmgl504 cellulase displayed activities at a broad range of temperature (25–55°C) and pH (5.5–8.5). The enzyme degraded carboxymethyl cellulose (CMC) with 15.4 U, while having low activity against avicel. No detectable activity was found for xylan and laminarin. The enzyme activity was stimulated by potassium chloride. The deduced protein and three-dimensional structure of metagenome-derived cellulase cmgl504 possessed all features, including general architecture, signature motifs, and N-terminal signal peptide, followed by the catalytic domain of cellulase belonging to glycosyl hydrolase family 5 (GHF5). The cellulases cloned in this work may play important roles in the degradation of celluloses in vermicomposting process and could be exploited for industrial application in future. 相似文献
205.
Zahid H. Chohan Humayun Pervez A. Rauf Khalid M. Khan Ghulam M. Maharvi 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):161-168
A new series of antibacterial and antifungal triazine-derived mono- and di-substituted (symmetrical and unsymmetrical) Schiff-bases and their cobalt(II), copper(II), nickel(II) and zinc(II) metal complexes have been synthesized and characterized by their elemental analyses, molar conductances, magnetic moments and IR and electronic spectral measurements. IR spectra indicated the ligands to act as tridentate towards divalent metal ions via a trazine-N, the azomethine-N and, indole-NH and deprotonated-O of salicylaldehyde. The magnetic moments and electronic spectral data suggest octahedral geometry for the Co(II), Ni(II) and Zn(II)complexes and square-pyramid for Cu(II) complexes. NMR spectral data of the ligands and their diamagnetic zinc(II) complexes well-define their proposed structures/geometries. Elemental analyses data of the ligands and metal complexes agree with their proposed structures/geometries. The synthesized ligands, along with their metal complexes were screened for their antibacterial activity against Escherichia coli, Bacillus subtillis, Shigella flexneri, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi and for antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. The results of these studies show the metal complexes to be more antibacterial/antifungal against two or more species as compared to the uncomplexed Schiff-base ligands. 相似文献
206.
Muhammad Nisar Inamullah Khan Bashir Ahmad Ihsan Ali Waqar Ahmad Muhammad Iqbal Choudhary 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):256-260
Current study was undertaken to evaluate the in vitro antifungal and antibacterial potential of methanol extract and subsequent fractions obtained after partitioning in organic solvents with variable polarity of the aerial parts of the tree Taxus wallichiana Zucc. Traditionally, this plant is often used in folk medicines in Pakistan for treating microbial infections. In order to rationalize the traditional use, methanol extracts of leaf, bark, and heartwood of Taxus wallichiana Zucc. were tested against six bacteria and six fungal strains using the Hole diffusion and macro-dilution methods. All extracts and fractions displayed significant antimicrobial effect. Only three fungal strains, Trichophyton longifusus, Microspoum canis, and Fusarium solani were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. In case of bacterial strains, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. Comparison results were carried out using imipinem, miconazole and amphotericin B as standard antibiotics. 相似文献
207.
Humayun Pervez Mohammad S. Iqbal Muhammad Younas Tahir Faiz-ul-Hassan Nasim Muhammad Iqbal Choudhary Khalid Mohammed Khan 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):848-854
A series of 15 previously reported N4-substituted isatin-3-thiosemicarbazones 3a-o has been screened for cytotoxic, antibacterial, antifungal and urease inhibitory activities. Compounds 3b, 3e and 3n proved to be active in cytotoxicity assay; 3e exhibited a high degree of cytotoxic activity (LD50 = 1.10 × 10? 5 M). Compound 3h exhibited significant antibacterial activity against B. subtilis, whereas compounds 3a, 3k and 3l displayed significant antifungal activity against one or more fungal strains i.e. T. longifusus, A. flavus and M. canis. In human urease enzyme inhibition assay, compounds 3g, 3k and 3m proved to be the most potent inhibitors, exhibiting relatively pronounced inhibition of the enzyme. These compounds, being non-toxic, could be potential candidates for orally effective therapeutic agents to treat certain clinical conditions induced by bacterial ureases like H. pylori urease. This study presents the first example of inhibition of urease by isatin-thiosemicarbazones and as such provides a solid basis for further research on such compounds to develop more potent inhibitors. 相似文献
208.
Muhammad Naeem Khan Muhammad Rasul Jan Jasmin Shah Sang Hak Lee Young Ho Kim 《Luminescence》2013,28(6):915-921
A highly sensitive and simple method for identifying sulpiride in pharmaceutical formulations and biological fluids is presented. The method is based on increased chemiluminescence (CL) intensity of a luminol–H2O2 system in response to the addition of Cr (III) under alkaline conditions. The CL intensity of the luminol–H2O2–Cr (III) system was greatly enhanced by the addition of sulpiride and the CL intensity was proportional to the concentration of sulpiride in a sample solution. Various parameters affecting the CL intensity were systematically investigated and optimized for determination of the sulpiride in a sample. Under the optimum conditions, the CL intensity was proportional to the concentration of sulpiride in the range of 0.068–4.0 µg/mL, with a good correlation coefficient of 0.997. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 8.50 × 10‐6 µg/mL and 2.83 × 10‐5 µg/mL, respectively. The method presented here produced good reproducibility with a relative standard deviation (RSD) of 2.70% (n = 7). The effects of common excipients and metal ions were studied for their interference effect. The method was validated statistically through recovery studies and successfully applied for the determination of sulpiride in pure form, pharmaceutical preparations and spiked human plasma samples. The percentage recoveries were found to range from 99.10 to 100.05% for pure form, 98.12 to 100.18% for pharmaceutical preparations and 97.9 to 101.4% for spiked human plasma. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
209.
Saif-ur-Rehman Khattak Dilnawaz Shaikh Iqbal Ahmad Khan Usmanghani Muhammad Ali Sheraz Sofia Ahmed 《AAPS PharmSciTech》2013,14(1):177-182
The effects of solvent [acetonitrile, methanol, and acetonitrile/water mixture (20:80, v/v)], buffer concentration (phosphate buffer, pH 7.5), ionic strength and commonly employed adjuvants on the photodegradation of betamethasone-17 valerate in cream and gel formulations have been studied on exposure to UV light (300–400 nm). A validated high-performance liquid chromatography method has been used to determine the parent compound and its photodegraded products. The photodegradation data in the studied solvents showed greater decomposition of the drug in solvents with a lower dielectric constant. A comparatively higher rate of photodegradation was observed in the cream formulation compared to that for the gel formulation. The kinetic treatment of the photodegradation data revealed that the degradation of the drug follows first-order kinetics and the apparent first-order rate constants for the photodegradation reactions, in the media studied, range from 1.62 to 11.30 × 10−3 min−1. The values of the rate constants decrease with increasing phosphate concentration and ionic strength which could be due to the deactivation of the excited state and radical quenching. The second-order rate constant (k′) for the phosphate ion-inhibited reactions at pH 7.5 has been found to be 5.22 × 10−2 M−1 s−1. An effective photostabilization of the drug has been achieved in cream and gel formulations with titanium dioxide (33.5–42.5%), vanillin (21.6–28.7%), and butyl hydroxytoluene (18.2–21.6%).Key words: betamethasone-17 valerate, creams and gels, kinetics, photodegradation, photostabilization 相似文献
210.