全文获取类型
收费全文 | 5630篇 |
免费 | 423篇 |
国内免费 | 547篇 |
专业分类
6600篇 |
出版年
2024年 | 14篇 |
2023年 | 85篇 |
2022年 | 194篇 |
2021年 | 364篇 |
2020年 | 243篇 |
2019年 | 267篇 |
2018年 | 285篇 |
2017年 | 204篇 |
2016年 | 258篇 |
2015年 | 355篇 |
2014年 | 427篇 |
2013年 | 432篇 |
2012年 | 539篇 |
2011年 | 470篇 |
2010年 | 288篇 |
2009年 | 273篇 |
2008年 | 286篇 |
2007年 | 258篇 |
2006年 | 199篇 |
2005年 | 145篇 |
2004年 | 163篇 |
2003年 | 135篇 |
2002年 | 91篇 |
2001年 | 76篇 |
2000年 | 78篇 |
1999年 | 73篇 |
1998年 | 43篇 |
1997年 | 46篇 |
1996年 | 46篇 |
1995年 | 40篇 |
1994年 | 29篇 |
1993年 | 27篇 |
1992年 | 26篇 |
1991年 | 17篇 |
1990年 | 17篇 |
1989年 | 19篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1979年 | 8篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1969年 | 2篇 |
1966年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有6600条查询结果,搜索用时 15 毫秒
31.
R L Bai K D Paull C L Herald L Malspeis G R Pettit E Hamel 《The Journal of biological chemistry》1991,266(24):15882-15889
Data generated in the new National Cancer Institute drug evaluation program, which is based on inhibition of cell growth in 60 human tumor cell lines, were used to compare new compounds with agents of known mechanism of action in terms of their differential cytotoxicity. Two marine natural products, halichondrin B and homohalichondrin B, appeared repeatedly when the data base was probed with known antimitotic agents. We confirmed that both compounds were highly cytotoxic (IC50 values for L1210 murine leukemia cells of 0.3 and 1 nM, respectively), with accumulation of cells arrested in mitosis at toxic concentrations, that both inhibited the polymerization of purified tubulin, and that both inhibited microtubule assembly dependent on microtubule-associated proteins. Limited amounts of homohalichondrin B, the less active agent, were available, so only halichondrin B was studied in detail. Halichondrin B did not interfere with colchicine binding to tubulin, but it was a noncompetitive inhibitor of the binding of vinblastine to tubulin (apparent Ki, 5.0 microM). Halichondrin B was therefore compared with other agents which interfere with the binding of vinca alkaloids to tubulin (vinblastine, maytansine, dolastatin 10, phomopsin A, rhizoxin) in terms of its effects on tubulin polymerization, inhibition of GTP hydrolysis, inhibition of nucleotide exchange, and stabilization of tubulin, as well as the quantitative assessment of its effects on vinca alkaloid binding and inhibition of cell growth. Since halichondrin B was originally isolated from the same organism as the phosphatase inhibitor okadaic acid, and since it is about 50-fold more effective than okadaic acid as an inhibitor of L1210 cell growth, perturbations of cellular microtubules observed following treatment with okadaic acid should be interpreted cautiously. 相似文献
32.
Cultured confluent human umbilical vein endothelial cells were irradiated in vitro with 60Co gamma rays at doses from 0 to 50 Gy. After irradiation thrombomodulin was measured at different times over 6 days in the supernatants of endothelial cell culture medium, on the surface of the cells, and within the cells. At 24 h after irradiation, an increase in the release of thrombomodulin from irradiated endothelial cells and an increase in the number of molecules and the activity of thrombomodulin on the surface of the cells were observed; these reactions were dependent on radiation dose. The capacity of the cells to produce and release thrombomodulin was decreased from 2 to 6 days after exposure to 60Co gamma rays. Our data indicate that radiation can injure endothelial cells, and that thrombomodulin may be used as a marker of radiation-induced injury in endothelial cells. The interrelationship between the dysfunction of irradiated endothelial cells and the pathological mechanisms of acute radiation disease is also discussed. 相似文献
33.
Testosterone and lipid metabolism was studied in rabbits. The effect of orchidectomy in rabbits fed normal diets and of testosterone propionate administration to these animals on total cholesterol, phospholipids, and triglycerides of serum, liver, aortic arch, thoracic aorta, and abdominal aorta as well as the activity of lipoprotein lipase in the aortic segments and heart was investigated. With a few exceptions, total cholesterol,phospholipids, and triglycerides increased in these tissues in orchidectomized animals and testosterone counteracted this increase. 3 segments of the aorta revealed variations in response to lipids in the orchidectomized animals as well as in the testosterone administered. Lipoprotein lipase activity decreased in the heart and the 3 aortic segments on orchidectomy, and testosterone administration caused increased enzyme activity. 相似文献
34.
35.
36.
Bo Qin Qian Bai Dan Yan Fanxiang Yin Zhu Zhu Chaoyuan Xia Yang Yang Yi Zhao 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1995
A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC50 value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer. 相似文献
37.
38.
流域季节性径流变化反映了年内水资源的动态特征。在以森林为主的流域中,森林变化和气候变异被普遍认为是影响流域水文过程的两大驱动因素。因此在全球气候变化背景下,研究流域森林恢复和气候变异对流域季节性径流的影响,可为协调区域碳-水关系和制订可持续的森林经营管理策略提供参考。选择鄱阳湖流域上游的平江流域为研究对象,根据流域历史森林覆盖率变化情况,将研究期划分为参考期(1961-1985)和森林恢复期(1986-2006),采用Mann-Kendall趋势分析研究流域长时期水文气象数据是否存在显著变化趋势。同时引入月干旱指数(潜在蒸散发和有效降雨的比率),将一年定义为能量限制季(1-6月)和水分限制季(7-12月),结合扩展的Budyko模型定量分析平江流域森林恢复和气候变异对季节性径流的相对贡献。在本研究流域整个研究期内(1961-2006),通过Mann-Kendall趋势分析发现,研究流域水分限制季径流呈现显著增加趋势,而能量限制季水文和气候变量变化趋势均不显著。其次,相较于参考期,流域森林恢复使能量限制季径流降低了11.71 mm/a (24.40%),使水分限制季径流增加了12.27 mm/a (17.23%)。同时,气候变异导致能量限制季径流减少了36.28 mm/a (75.60%),而使水分限制季径流增加了58.94 mm/a (82.77%)。上述研究结果表明,森林恢复对径流影响具有累积效应。森林恢复对季节性径流具有积极的调节作用,同时季节性径流对森林恢复的响应存在时间差,而且森林恢复对径流的影响在能量限制季和水分限制季具有相互抵消的作用,气候变异与森林恢复的影响效应类似。此外,本研究也证实,平江流域季节性径流变化主要是受气候变化主导,但森林恢复对季节性径流的贡献也不容忽视。 相似文献
39.
40.
基于高通量测序技术对山羊盲肠细菌多样性的分析 总被引:4,自引:0,他引:4
【背景】由于反刍动物特殊的生理结构,以往研究者主要集中对其瘤胃微生物的结构与组成进行了大量研究,严重忽略了盲肠微生物在营养物质消化和肠道健康方面发挥的重要作用。【目的】采用高通量测序技术分析山羊盲肠细菌的多样性及菌群结构。【方法】选用12只10月龄健康母羊,其平均体重为20.70±1.60kg,饲喂20d后,采集每只山羊的盲肠内容物,提取微生物总DNA,用细菌通用引物对细菌16S rRNA基因的高可变区进行PCR扩增,利用Illumina MiSeq平台对扩增子进行高通量测序,并用QIIME等软件对测序序列进行生物信息学分析。【结果】山羊盲肠微生物测序共获得813 496条有效序列与6 883个OTU,并且稀释曲线和Coverage指数反映此次测序结果比较全面的覆盖了山羊盲肠微生物群落。α多样性和β多样性分析表明,山羊个体之间盲肠微生物的多样性存在差异。在门水平,各样品的优势菌门均为厚壁菌门(Firmicutes)和拟杆菌门(Bacteroidetes);属水平,核心菌群由梭菌属(Clostridium)、瘤胃球菌属(Ruminococcus)和6个未分类的细菌组成。PICRUSt基因预测表明,山羊盲肠微生物以代谢功能为主,主要包括:碳水化合物代谢、氨基酸代谢、能量代谢和脂质代谢等。【结论】山羊盲肠与瘤胃细菌的多样性存在显著差异,与粪便微生物组成相似;与单胃动物相比,两者盲肠微生物的组成既有共性,也存在差异。 相似文献