全文获取类型
收费全文 | 64篇 |
免费 | 0篇 |
专业分类
系统科学 | 2篇 |
理论与方法论 | 4篇 |
现状及发展 | 21篇 |
研究方法 | 12篇 |
综合类 | 24篇 |
自然研究 | 1篇 |
出版年
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 1篇 |
2014年 | 1篇 |
2012年 | 3篇 |
2011年 | 10篇 |
2010年 | 2篇 |
2009年 | 1篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 1篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2002年 | 8篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1989年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有64条查询结果,搜索用时 15 毫秒
61.
Braig M Lee S Loddenkemper C Rudolph C Peters AH Schlegelberger B Stein H Dörken B Jenuwein T Schmitt CA 《Nature》2005,436(7051):660-665
Acute induction of oncogenic Ras provokes cellular senescence involving the retinoblastoma (Rb) pathway, but the tumour suppressive potential of senescence in vivo remains elusive. Recently, Rb-mediated silencing of growth-promoting genes by heterochromatin formation associated with methylation of histone H3 lysine 9 (H3K9me) was identified as a critical feature of cellular senescence, which may depend on the histone methyltransferase Suv39h1. Here we show that Emicro-N-Ras transgenic mice harbouring targeted heterozygous lesions at the Suv39h1, or the p53 locus for comparison, succumb to invasive T-cell lymphomas that lack expression of Suv39h1 or p53, respectively. By contrast, most N-Ras-transgenic wild-type ('control') animals develop a non-lymphoid neoplasia significantly later. Proliferation of primary lymphocytes is directly stalled by a Suv39h1-dependent, H3K9me-related senescent growth arrest in response to oncogenic Ras, thereby cancelling lymphomagenesis at an initial step. Suv39h1-deficient lymphoma cells grow rapidly but, unlike p53-deficient cells, remain highly susceptible to adriamycin-induced apoptosis. In contrast, only control, but not Suv39h1-deficient or p53-deficient, lymphomas senesce after drug therapy when apoptosis is blocked. These results identify H3K9me-mediated senescence as a novel Suv39h1-dependent tumour suppressor mechanism whose inactivation permits the formation of aggressive but apoptosis-competent lymphomas in response to oncogenic Ras. 相似文献
62.
Niederreither K Abu-Abed S Schuhbaur B Petkovich M Chambon P Dollé P 《Nature genetics》2002,31(1):84-88
Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that acts in developing and adult tissues. The Cyp26a1 (cytochrome p450, 26) protein metabolizes retinoic acid into more polar hydroxylated and oxidized derivatives. Whether some of these derivatives are biologically active metabolites has been debated. Cyp26a1(-/-) mouse fetuses have lethal morphogenetic phenotypes mimicking those generated by excess retinoic acid administration, indicating that human CYP26A1 may be essential in controlling retinoic acid levels during development. This hypothesis suggests that the Cyp26a1(-/-) phenotype could be rescued under conditions in which embryonic retinoic acid levels are decreased. We show that Cyp26a1(-/-) mice are phenotypically rescued by heterozygous disruption of Aldh1a2 (also known as Raldh2), which encodes a retinaldehyde dehydrogenase responsible for the synthesis of retinoic acid during early embryonic development. Aldh1a2 haploinsufficiency prevents the appearance of spina bifida and rescues the development of posterior structures (sacral/caudal vertebrae, hindgut, urogenital tract), while partly preventing cervical vertebral transformations and hindbrain pattern alterations in Cyp26a1(-/-) mice. Thus, some of these double-mutant mice can reach adulthood. This study is the first report of a mutation acting as a dominant suppressor of a lethal morphogenetic mutation in mammals. We provide genetic evidence that ALDH1A2 and CYP26A1 activities concurrently establish local embryonic retinoic acid levels that must be finely tuned to allow posterior organ development and to prevent spina bifida. 相似文献
63.
64.
Brigitte Ziegler R. Butter H. -J. Hahn R. Mehling H. Fiedler 《Cellular and molecular life sciences : CMLS》1973,29(7):881-882
Zusammenfassung Inseln adulter Wistarratten wurden auf Glasfaservlies auf Metallgitter unter den Bedingungen der Organkultur gezüchtet und der Einfluss der Inselzahl unter basalen und stimulierten Bedingungen auf die Insulinsekretion in 24 h-Perioden während der Kultivierung untersucht. 相似文献