全文获取类型
收费全文 | 126篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
丛书文集 | 2篇 |
现状及发展 | 34篇 |
研究方法 | 24篇 |
综合类 | 62篇 |
自然研究 | 5篇 |
出版年
2021年 | 2篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 2篇 |
2015年 | 1篇 |
2014年 | 1篇 |
2013年 | 6篇 |
2012年 | 13篇 |
2011年 | 15篇 |
2010年 | 6篇 |
2008年 | 8篇 |
2007年 | 13篇 |
2006年 | 15篇 |
2005年 | 7篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 7篇 |
1999年 | 1篇 |
1992年 | 1篇 |
1981年 | 3篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1959年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有127条查询结果,搜索用时 0 毫秒
51.
Suh EK Yang A Kettenbach A Bamberger C Michaelis AH Zhu Z Elvin JA Bronson RT Crum CP McKeon F 《Nature》2006,444(7119):624-628
Meiosis in the female germ line of mammals is distinguished by a prolonged arrest in prophase of meiosis I between homologous chromosome recombination and ovulation. How DNA damage is detected in these arrested oocytes is poorly understood, but it is variably thought to involve p53, a central tumour suppressor in mammals. While the function of p53 in monitoring the genome of somatic cells is clear, a consensus for the importance of p53 for germ line integrity has yet to emerge. Here we show that the p53 homologue p63 (refs 5, 6), and specifically the TAp63 isoform, is constitutively expressed in female germ cells during meiotic arrest and is essential in a process of DNA damage-induced oocyte death not involving p53. We also show that DNA damage induces both the phosphorylation of p63 and its binding to p53 cognate DNA sites and that these events are linked to oocyte death. Our data support a model whereby p63 is the primordial member of the p53 family and acts in a conserved process of monitoring the integrity of the female germ line, whereas the functions of p53 are restricted to vertebrate somatic cells for tumour suppression. These findings have implications for understanding female germ line fidelity, the regulation of fertility and the evolution of tumour suppressor mechanisms. 相似文献
52.
1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic or teichoic acids (TA),namely:-(C)n-O-PO-,where n=2 (for teichoic acids) or 3.These methods,to be discussed in the lecture,are based on the ring-opening polymerization,transesterification,and recently elaborated direct addition of phosphoric acid to diepoxides.For the first time an attempt h... 相似文献
53.
Suppression of inflammation by a synthetic histone mimic 总被引:1,自引:0,他引:1
Nicodeme E Jeffrey KL Schaefer U Beinke S Dewell S Chung CW Chandwani R Marazzi I Wilson P Coste H White J Kirilovsky J Rice CM Lora JM Prinjha RK Lee K Tarakhovsky A 《Nature》2010,468(7327):1119-1123
54.
Vivek S. Peche Tad A. Holak Bhagyashri D. Burgute Kosmas Kosmas Sushant P. Kale F. Thomas Wunderlich Fatiha Elhamine Robert Stehle Gabriele Pfitzer Klaus Nohroudi Klaus Addicks Florian Stöckigt Jan W. Schrickel Julia Gallinger Michael Schleicher Angelika A. Noegel 《Cellular and molecular life sciences : CMLS》2017,74(21):4045-4045
55.
Serena Stadler Chi Huu Nguyen Helga Schachner Daniela Milovanovic Silvio Holzner Stefan Brenner Julia Eichsteininger Mira Stadler Daniel Senfter Liselotte Krenn Wolfgang M. Schmidt Nicole Huttary Sigurd Krieger Oskar Koperek Zsuzsanna Bago-Horvath Konstantin Alexander Brendel Brigitte Marian Oliver de Wever Robert M. Mader Benedikt Giessrigl Walter Jäger Helmut Dolznig Georg Krupitza 《Cellular and molecular life sciences : CMLS》2017,74(10):1907-1921
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca2+ levels were measured and pharmacological- or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca2+, Ca2+-calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca2+ release. Thus, Ca2+ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour–stroma interaction. 相似文献
56.
57.
Copeland SR Sponheimer M de Ruiter DJ Lee-Thorp JA Codron D le Roux PJ Grimes V Richards MP 《Nature》2011,474(7349):76-78
Ranging and residence patterns among early hominins have been indirectly inferred from morphology, stone-tool sourcing, referential models and phylogenetic models. However, the highly uncertain nature of such reconstructions limits our understanding of early hominin ecology, biology, social structure and evolution. We investigated landscape use in Australopithecus africanus and Paranthropus robustus from the Sterkfontein and Swartkrans cave sites in South Africa using strontium isotope analysis, a method that can help to identify the geological substrate on which an animal lived during tooth mineralization. Here we show that a higher proportion of small hominins than large hominins had non-local strontium isotope compositions. Given the relatively high levels of sexual dimorphism in early hominins, the smaller teeth are likely to represent female individuals, thus indicating that females were more likely than males to disperse from their natal groups. This is similar to the dispersal pattern found in chimpanzees, bonobos and many human groups, but dissimilar from that of most gorillas and other primates. The small proportion of demonstrably non-local large hominin individuals could indicate that male australopiths had relatively small home ranges, or that they preferred dolomitic landscapes. 相似文献
58.
Gibbs DJ Lee SC Isa NM Gramuglia S Fukao T Bassel GW Correia CS Corbineau F Theodoulou FL Bailey-Serres J Holdsworth MJ 《Nature》2011,479(7373):415-418
59.
Yokoyama S Woods SL Boyle GM Aoude LG MacGregor S Zismann V Gartside M Cust AE Haq R Harland M Taylor JC Duffy DL Holohan K Dutton-Regester K Palmer JM Bonazzi V Stark MS Symmons J Law MH Schmidt C Lanagan C O'Connor L Holland EA Schmid H Maskiell JA Jetann J Ferguson M Jenkins MA Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Whiteman DC Pharoah PD Easton DF Dunning AM Newton-Bishop JA Montgomery GW Martin NG Mann GJ Bishop DT Tsao H Trent JM Fisher DE Hayward NK Brown KM 《Nature》2011,480(7375):99-103
60.
Humans actively share resources with one another to a much greater degree than do other great apes, and much human sharing is governed by social norms of fairness and equity. When in receipt of a windfall of resources, human children begin showing tendencies towards equitable distribution with others at five to seven years of age. Arguably, however, the primordial situation for human sharing of resources is that which follows cooperative activities such as collaborative foraging, when several individuals must share the spoils of their joint efforts. Here we show that children of around three years of age share with others much more equitably in collaborative activities than they do in either windfall or parallel-work situations. By contrast, one of humans' two nearest primate relatives, chimpanzees (Pan troglodytes), 'share' (make food available to another individual) just as often whether they have collaborated with them or not. This species difference raises the possibility that humans' tendency to distribute resources equitably may have its evolutionary roots in the sharing of spoils after collaborative efforts. 相似文献