全文获取类型
收费全文 | 657篇 |
免费 | 47篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 19篇 |
2020年 | 5篇 |
2019年 | 13篇 |
2018年 | 10篇 |
2017年 | 7篇 |
2016年 | 16篇 |
2015年 | 24篇 |
2014年 | 23篇 |
2013年 | 26篇 |
2012年 | 38篇 |
2011年 | 39篇 |
2010年 | 30篇 |
2009年 | 18篇 |
2008年 | 31篇 |
2007年 | 28篇 |
2006年 | 24篇 |
2005年 | 40篇 |
2004年 | 29篇 |
2003年 | 26篇 |
2002年 | 21篇 |
2001年 | 14篇 |
2000年 | 11篇 |
1999年 | 18篇 |
1998年 | 5篇 |
1997年 | 13篇 |
1996年 | 6篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 10篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 14篇 |
1988年 | 13篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 16篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1974年 | 6篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1970年 | 4篇 |
1949年 | 2篇 |
排序方式: 共有704条查询结果,搜索用时 480 毫秒
61.
Skp2B stimulates mammary gland development by inhibiting REA, the repressor of the estrogen receptor
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Umanskaya K Radke S Chander H Monardo R Xu X Pan ZQ O'Connell MJ Germain D 《Molecular and cellular biology》2007,27(21):7615-7622
Skp2B, an F-box protein of unknown function, is frequently overexpressed in breast cancer. In order to determine the function of Skp2B and whether it has a role in breast cancer, we performed a two-hybrid screen and established transgenic mice expressing Skp2B in the mammary glands. We found that Skp2B interacts with the repressor of estrogen receptor activity (REA) and that overexpression of Skp2B leads to a reduction in REA levels. In the mammary glands of MMTV-Skp2B mice, REA levels are also low. Our results show that in virgin transgenic females, Skp2B induces lobuloalveolar development and differentiation of the mammary glands normally observed during pregnancy. As this phenotype is identical to what was observed for REA heterozygote mice, our observations suggest that the Skp2B-REA interaction is physiologically relevant. However, in contrast to REA(+/-) mice, MMTV-Skp2B mice develop mammary tumors, suggesting that Skp2B affects additional proteins. These results indicate that the observed expression of Skp2B in breast cancer does contribute to tumorigenesis at least in part by modulating the activity of the estrogen receptor. 相似文献
62.
63.
64.
Anna R Batt Commodore P St Germain Trevor Gokey Anton B Guliaev Teaster Baird Jr 《Protein science : a publication of the Protein Society》2015,24(9):1463-1474
The development of effective protease therapeutics requires that the proteases be more resistant to naturally occurring inhibitors while maintaining catalytic activity. A key step in developing inhibitor resistance is the identification of key residues in protease-inhibitor interaction. Given that majority of the protease therapeutics currently in use are trypsin-fold, trypsin itself serves as an ideal model for studying protease-inhibitor interaction. To test the importance of several trypsin-inhibitor interactions on the prime-side binding interface, we created four trypsin single variants Y39A, Y39F, K60A, and K60V and report biochemical sensitivity against bovine pancreatic trypsin inhibitor (BPTI) and M84R ecotin. All variants retained catalytic activity against small, commercially available peptide substrates [kcat/KM = (1.2 ± 0.3) × 107 M−1 s−1. Compared with wild-type, the K60A and K60V variants showed increased sensitivity to BPTI but less sensitivity to ecotin. The Y39A variant was less sensitive to BPTI and ecotin while the Y39F variant was more sensitive to both. The relative binding free energies between BPTI complexes with WT, Y39F, and Y39A were calculated based on 3.5 µs combined explicit solvent molecular dynamics simulations. The BPTI:Y39F complex resulted in the lowest binding energy, while BPTI:Y39A resulted in the highest. Simulations of Y39F revealed increased conformational rearrangement of F39, which allowed formation of a new hydrogen bond between BPTI R17 and H40 of the variant. All together, these data suggest that positions 39 and 60 are key for inhibitor binding to trypsin, and likely more trypsin-fold proteases. 相似文献
65.
66.
Jane M. Reid Peter Arcese Lukas F. Keller Ryan R. Germain A. Bradley Duthie Sylvain Losdat Matthew E. Wolak Pirmin Nietlisbach 《Evolution; international journal of organic evolution》2015,69(1):59-74
Extra-pair reproduction is widely hypothesized to allow females to avoid inbreeding with related socially paired males. Consequently, numerous field studies have tested the key predictions that extra-pair offspring are less inbred than females’ alternative within-pair offspring, and that the probability of extra-pair reproduction increases with a female's relatedness to her socially paired male. However, such studies rarely measure inbreeding or relatedness sufficiently precisely to detect subtle effects, or consider biases stemming from failure to observe inbred offspring that die during early development. Analyses of multigenerational song sparrow (Melospiza melodia) pedigree data showed that most females had opportunity to increase or decrease the coefficient of inbreeding of their offspring through extra-pair reproduction with neighboring males. In practice, observed extra-pair offspring had lower inbreeding coefficients than females’ within-pair offspring on average, while the probability of extra-pair reproduction increased substantially with the coefficient of kinship between a female and her socially paired male. However, simulations showed that such effects could simply reflect bias stemming from inbreeding depression in early offspring survival. The null hypothesis that extra-pair reproduction is random with respect to kinship therefore cannot be definitively rejected in song sparrows, and existing general evidence that females avoid inbreeding through extra-pair reproduction requires reevaluation given such biases. 相似文献
67.
68.
Sandra Belboom Robert Renzoni Benoît Verjans Angélique Léonard Albert Germain 《The International Journal of Life Cycle Assessment》2011,16(2):159-167
Purpose
This study compares environmental impacts of two primary packaging alternatives used for injectable drugs: the traditional method based on glass vials and the method developed by Aseptic Technologies based on polymer vials. A critical review by an external LCA expert was made. 相似文献69.
70.