全文获取类型
收费全文 | 555篇 |
免费 | 56篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 7篇 |
2019年 | 8篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 13篇 |
2015年 | 23篇 |
2014年 | 30篇 |
2013年 | 24篇 |
2012年 | 35篇 |
2011年 | 29篇 |
2010年 | 16篇 |
2009年 | 24篇 |
2008年 | 25篇 |
2007年 | 25篇 |
2006年 | 14篇 |
2005年 | 25篇 |
2004年 | 14篇 |
2003年 | 15篇 |
2002年 | 18篇 |
2001年 | 13篇 |
2000年 | 17篇 |
1999年 | 12篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1979年 | 7篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1964年 | 3篇 |
1955年 | 3篇 |
1938年 | 6篇 |
1933年 | 3篇 |
排序方式: 共有611条查询结果,搜索用时 15 毫秒
91.
Elke EM Brouwers Alwin DR Huitema Jos H Beijnen Jan HM Schellens 《BMC clinical pharmacology》2008,8(1):7
Background
The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin. 相似文献92.
93.
94.
95.
96.
Equilibrium binding of Hoechst 33258 and Hoechst 33342 fluorochromes with rat colorectal cells 总被引:1,自引:0,他引:1
P F McGowan R E Hurst R A Bass L J Wilcox G P Hemstreet R G Postier 《The journal of histochemistry and cytochemistry》1988,36(7):757-762
We examined the biophysical characteristics of the interaction of Hoechst 33258 and 33342 dyes with normal rat colorectal cells as functions of fixation and solution composition. Classical dye-binding techniques were used to investigate the stoichiometry and binding constants with whole cells, and quantitative fluorescence image analysis was used to specifically study nuclear dye binding in intact cells. In aqueous solution, H-33258 dye bound cooperatively with intact cells, with a binding constant of between 3-4 x 10(5). In ethanolic solution, binding appeared less cooperative, although Scatchard analysis could not be used. The binding constant was slightly lower (2 x 10(5)), but the total number of cell binding sites was decreased by a factor of 5, reflecting a great decrease in cytoplasmic sites. QFIA studies identified conditions optimal for DNA quantitation under which the fluorescence signal was independent of dye or cell concentration. The proportionality between absolute nuclear fluorescence intensity and DNA content was established, and the upper limit of DNA content of normal colorectal cells was also determined. 相似文献
97.
Evidence for the regulation of exocytic transport by protein phosphorylation 总被引:13,自引:7,他引:6 下载免费PDF全文
We investigated the effects of the protein phosphatase inhibitors okadaic acid and microcystin-LR upon transport of newly synthesized proteins through the exocytic pathway. Treatment of CHO cells with 1 microM okadaic acid rapidly inhibited movement of a marker protein (vesicular stomatitis virus G protein) from the endoplasmic reticulum to the Golgi compartment. Both okadaic acid and microcystin-LR also inhibited transport in an in vitro assay reconstituting movement to the Golgi compartment, at concentrations equivalent to those required to inhibit phosphorylase phosphatase activity. Inhibition both in vivo and in vitro could be antagonized by protein kinase inhibitors, suggesting that protein phosphorylation was directly responsible for this effect. An early stage in the transport reaction associated with vesicle formation or targeting was inhibited by protein phosphorylation, which could be reversed by fractions enriched in protein phosphatase 2A. Protein kinase antagonists did not inhibit transport between sequential compartments of the exocytic pathway in vitro, suggesting that protein phosphorylation is not itself required for vesicular transport. During mitosis, vesicular transport is inhibited simultaneous to the activation of maturation-promoting factor. It is proposed that the inhibition caused by okadaic acid and microcystin-LR involves a similar mechanism to that responsible for the mitotic arrest of vesicular transport. 相似文献
98.
The genetics of sympatric Arctic charr [Salvelinus alpinus (L.)] populations from Loch Rannoch, Scotland 总被引:3,自引:0,他引:3
S. E. Hartley C. McGowan † R. B. Greek † A. F. Walker ‡ 《Journal of fish biology》1992,41(6):1021-1031
Two morphologically and ecologically distinct forms of Arctic charr, Salvelinus alpinus , are found in Loch Rannoch, Scotland. The differences in morphology are adaptations to different modes of life, one being pelagic, the other benthic. Both forms have been the subjects of extensive genetic studies including cytogenetics, nuclear and mitochondrial DNA analysis, and protein electrophoresis. Significant differences between the two forms are revealed by some techniques but not others and provide evidence for the reproductive isolation of these two morphs. The findings are discussed in relation to the derivation of sympatry and the phylogenetics of Arctic charr. 相似文献
99.
Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. 总被引:72,自引:0,他引:72
L Chen S Ashe W A Brady I Hellstr?m K E Hellstr?m J A Ledbetter P McGowan P S Linsley 《Cell》1992,71(7):1093-1102
Interaction of the B7 molecule on antigen-presenting cells with its receptors CD28 and CTLA-4 on T cells provides costimulatory signals for T cell activation. We have studied the effects of B7 on antitumor immunity to a murine melanoma that expresses a rejection antigen associated with the E7 gene product of human papillomavirus 16. While this E7+ tumor grows progressively in immunocompetent hosts, cotransfection of its cells with B7 led to tumor regression by a B7-dependent immune response mediated by CD8+ cytolytic T lymphocytes. The immune response induced by E7+B7+ tumor cells also caused regression of E7+B7- tumors at distant sites and was curative for established E7+B7- micrometastases. Our findings suggest that increasing T cell costimulation through the CD28 and CTLA-4 receptors may have therapeutic usefulness for generating immunity against tumors expressing viral antigens. 相似文献
100.
David C. McGowan Florence Herschke Mourad D. Khamlichi Mari Luz Rosauro Sara M. Pérez Benedicto Frederik Pauwels Bart Stoops Vineet Pande Annick Scholliers Bertrand Van Schoubroeck Wendy Mostmans Kris Van Dijck Tine Thoné Helen Horton Gregory Fanning Tim H.M. Jonckers Pierre Raboisson 《Bioorganic & medicinal chemistry letters》2018,28(19):3216-3221
In a continuing effort to discover novel TLR agonists, herein we report on the discovery and structure–activity relationship of novel tetrahydropyridopyrimidine TLR 7/8 agonists. Optimization of this series towards dual agonist activity and a high clearance profile resulted in the identification of compound 52a1. Evaluation in vivo revealed an interferon stimulated response (ISG) in mice with limited systemic exposure and demonstrated the potential in antiviral treatment or as a vaccine adjuvant. 相似文献