全文获取类型
收费全文 | 210篇 |
免费 | 0篇 |
专业分类
现状及发展 | 11篇 |
研究方法 | 39篇 |
综合类 | 160篇 |
出版年
2012年 | 20篇 |
2011年 | 22篇 |
2010年 | 6篇 |
2008年 | 11篇 |
2007年 | 9篇 |
2006年 | 12篇 |
2005年 | 11篇 |
2004年 | 14篇 |
2003年 | 18篇 |
2002年 | 14篇 |
2001年 | 7篇 |
2000年 | 13篇 |
1999年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1977年 | 1篇 |
1971年 | 5篇 |
1970年 | 8篇 |
1966年 | 1篇 |
1959年 | 2篇 |
1958年 | 9篇 |
1957年 | 3篇 |
1956年 | 4篇 |
1955年 | 3篇 |
1954年 | 3篇 |
1948年 | 4篇 |
1947年 | 1篇 |
排序方式: 共有210条查询结果,搜索用时 390 毫秒
61.
Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1 总被引:26,自引:0,他引:26
Li YM Xu M Lai MT Huang Q Castro JL DiMuzio-Mower J Harrison T Lellis C Nadin A Neduvelil JG Register RB Sardana MK Shearman MS Smith AL Shi XP Yin KC Shafer JA Gardell SJ 《Nature》2000,405(6787):689-694
Cleavage of amyloid precursor protein (APP) by the beta- and gamma-secretases generates the amino and carboxy termini, respectively, of the A beta amyloidogenic peptides A beta40 and A beta42--the major constituents of the amyloid plaques in the brain parenchyma of Alzheimer's disease patients. There is evidence that the polytopic membrane-spanning proteins, presenilin 1 and 2 (PS1 and PS2), are important determinants of gamma-secretase activity: mutations in PS1 and PS2 that are associated with early-onset familial Alzheimer's disease increase the production of A beta42 (refs 4-6), the more amyloidogenic peptide; gamma-secretase activity is reduced in neuronal cultures derived from PS1-deficient mouse embryos; and directed mutagenesis of two conserved aspartates in transmembrane segments of PS1 inactivates the ability of gamma-secretase to catalyse processing of APP within its transmembrane domain. It is unknown, however, whether PS1 (which has little or no homology to any known aspartyl protease) is itself a transmembrane aspartyl protease or a gamma-secretase cofactor, or helps to colocalize gamma-secretase and APP. Here we report photoaffinity labelling of PS1 (and PS2) by potent gamma-secretase inhibitors that were designed to function as transition state analogue inhibitors directed to the active site of an aspartyl protease. This observation indicates that PS1 (and PS2) may contain the active site of gamma-secretase. Interestingly, the intact, single-chain form of wild-type PS1 is not labelled by an active-site-directed photoaffinity probe, suggesting that intact wild-type PS1 may be an aspartyl protease zymogen. 相似文献
62.
63.
64.
65.
66.
67.
68.
A step towards global key distribution 总被引:1,自引:0,他引:1
Kurtsiefer C Zarda P Halder M Weinfurter H Gorman PM Tapster PR Rarity JG 《Nature》2002,419(6906):450
Large random bit-strings known as 'keys' are used to encode and decode sensitive data, and the secure distribution of these keys is essential to secure communications across the globe. Absolutely secure key exchange between two sites has now been demonstrated over fibre and free-space optical links. Here we describe the secure exchange of keys over a free-space path of 23.4 kilometres between two mountains. This marks a step towards accomplishing key exchange with a near-Earth orbiting satellite and hence a global key-distribution system. 相似文献
69.
Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours 总被引:22,自引:0,他引:22
Malliri A van der Kammen RA Clark K van der Valk M Michiels F Collard JG 《Nature》2002,417(6891):867-871
70.