全文获取类型
收费全文 | 1942篇 |
免费 | 125篇 |
出版年
2021年 | 29篇 |
2020年 | 14篇 |
2019年 | 19篇 |
2018年 | 27篇 |
2017年 | 21篇 |
2016年 | 37篇 |
2015年 | 66篇 |
2014年 | 85篇 |
2013年 | 125篇 |
2012年 | 132篇 |
2011年 | 133篇 |
2010年 | 73篇 |
2009年 | 71篇 |
2008年 | 97篇 |
2007年 | 119篇 |
2006年 | 98篇 |
2005年 | 103篇 |
2004年 | 97篇 |
2003年 | 103篇 |
2002年 | 78篇 |
2001年 | 26篇 |
2000年 | 10篇 |
1999年 | 15篇 |
1998年 | 27篇 |
1997年 | 23篇 |
1996年 | 22篇 |
1995年 | 16篇 |
1994年 | 17篇 |
1993年 | 20篇 |
1992年 | 22篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 17篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 17篇 |
1984年 | 20篇 |
1983年 | 11篇 |
1982年 | 20篇 |
1981年 | 17篇 |
1978年 | 15篇 |
1977年 | 8篇 |
1976年 | 10篇 |
1975年 | 10篇 |
1974年 | 17篇 |
1973年 | 8篇 |
1972年 | 10篇 |
1965年 | 7篇 |
1948年 | 8篇 |
排序方式: 共有2067条查询结果,搜索用时 368 毫秒
51.
Andrea J. Hartlerode Yinghua Guan Anbazhagan Rajendran Kiyoe Ura Gunnar Schotta Anyong Xie Jagesh V. Shah Ralph Scully 《PloS one》2012,7(11)
Recruitment of 53BP1 to chromatin flanking double strand breaks (DSBs) requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me). Several histone methyltransferases have been implicated in 53BP1 recruitment, but their quantitative contributions to the 53BP1 response are unclear. We have developed a multi-photon laser (MPL) system to target DSBs to subfemtoliter nuclear volumes and used this to mathematically model DSB response kinetics of MDC1 and of 53BP1. In contrast to MDC1, which revealed first order kinetics, the 53BP1 MPL-DSB response is best fitted by a Gompertz growth function. The 53BP1 MPL response shows the expected dependency on MDC1 and RNF8. We determined the impact of altered H4K20 methylation on 53BP1 MPL response kinetics in mouse embryonic fibroblasts (MEFs) lacking key H4K20 histone methyltransferases. This revealed no major requirement for the known H4K20 dimethylases Suv4-20h1 and Suv4-20h2 in 53BP1 recruitment or DSB repair function, but a key role for the H4K20 monomethylase, PR-SET7. The histone methyltransferase MMSET/WHSC1 has recently been implicated in 53BP1 DSB recruitment. We found that WHSC1 homozygous mutant MEFs reveal an alteration in balance of H4K20 methylation patterns; however, 53BP1 DSB responses in these cells appear normal. 相似文献
52.
Statistical physicists have become interested in models of collective social behavior such as opinion formation, where individuals change their inherently preferred opinion if their friends disagree. Real preferences often depend on regional cultural differences, which we model here as a spatial gradient g in the initial opinion. The gradient does not only add reality to the model. It can also reveal that opinion clusters in two dimensions are typically in the standard (i.e., independent) percolation universality class, thus settling a recent controversy about a non-consensus model. However, using analytical and numerical tools, we also present a model where the width of the transition between opinions scales , not as in independent percolation, and the cluster size distribution is consistent with first-order percolation. 相似文献
53.
54.
55.
56.
57.
Christopher J. Fowler Sandra Holt Gunnar Tiger 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):55-58
Previous studies have demonstrated that fatty acid amide hydrolase, the enzyme responsible for the metabolism of anandamide, is inhibited by the acidic non-steroidal anti-inflammatory drug (NSAID) ibuprofen with a potency that increases as the assay pH is reduced. Here we show that (R) -, (S) - and (R, S) -flurbiprofen, indomethacin and niflumic acid show similar pH-dependent shifts in potency to that seen with ibuprofen. Thus, (S) -flurbiprofen inhibited 2 μM [3 H]anandamide metabolism with IC 50 values of 13 and 50 μM at assay pH values of 6 and 8, respectively. In contrast, the neutral compound celecoxib was a weak fatty acid amide hydrolase inhibitor and showed no pH dependency (IC 50 values ~300 μM at both assay pH). The cyclooxygenase-2-selective inhibitors nimesulide and SC-58125 did not inhibit fatty acid amide hydrolase activity at either pH. The data are consistent with the conclusion that the non-ionised forms of the acidic NSAIDs are responsible for the inhibition of fatty acid amide hydrolase. 相似文献
58.
Christopher J. Fowler Gunnar Tiger María L. López-Rodríguez Alma Viso Silvia Ortega-Gutiérrez José A. Ramos 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):225-231
Arachidonoyl-serotonin inhibits in a mixed-type manner the metabolism of the endocannabinoid anandamide by the enzyme fatty acid amidohydrolase. In the present study, compounds related to arachidonoyl-serotonin have been synthesised and investigated for their ability to inhibit anandamide hydrolysis by this enzyme in rat brain homogenates. Removal of the 5-hydroxy from the serotonin head group of arachidonoyl-serotonin produced a compound (N-arachidonoyltryptamine) that was a 2.3-fold weaker inhibitor of anandamide hydrolysis, but which also produced its inhibition by a mixed-type manner (Ki(slope) 1.3 µM; Ki(intercept) 44 µM). Replacement of the amide linkage in this compound by an ester group further reduced the potency. In contrast, replacement of the arachidonoyl side chain by a linolenoyl side chain did not affect the observed potency. N-(Fur-3-ylmethyl) arachidonamide (UCM707), N-(fur-3-ylmethyl)linolenamide and N-(fur-3-ylmethyl)oleamide inhibited anandamide hydrolysis with pI50 values of 4.53, 5.36 and 5.25, respectively. The linolenamide derivative was also found to be a mixed-type inhibitor. It is concluded that the 5-hydroxy group of arachidonoyl-serotonin contributes to, but is not essential for, inhibitory potency at fatty acid amidohydrolase. 相似文献
59.
60.
Kristin Stamyr Olavi Vaittinen Janne Jaakola Joseph Guss Markus Metsälä Gunnar Johanson 《Biomarkers》2013,18(5):285-291
Hydrogen cyanide (HCN) in breath has been suggested as a diagnostic tool for cyanide poisoning and for cyanide-producing bacterial infections. To distinguish elevated levels of breath HCN, baseline data are needed. Background levels of HCN were measured in mixed exhaled air from 40 healthy subjects (26 men, 14 women, age 21–61 years; detection limit: 1.5?ppb; median: 4.4?ppb; range <1.5–14?ppb) by near-infrared cavity ring down spectroscopy (CRDS). No correlation was observed with smoking habits, recent meals or age. However, female subjects had slightly higher breath levels of HCN than male subjects. CRDS has not previously been used for this purpose. 相似文献