全文获取类型
收费全文 | 85篇 |
免费 | 0篇 |
专业分类
理论与方法论 | 3篇 |
现状及发展 | 7篇 |
研究方法 | 29篇 |
综合类 | 44篇 |
自然研究 | 2篇 |
出版年
2021年 | 1篇 |
2013年 | 1篇 |
2012年 | 5篇 |
2011年 | 8篇 |
2010年 | 2篇 |
2008年 | 6篇 |
2007年 | 8篇 |
2006年 | 7篇 |
2005年 | 4篇 |
2004年 | 2篇 |
2003年 | 3篇 |
2002年 | 6篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1973年 | 2篇 |
1970年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有85条查询结果,搜索用时 15 毫秒
41.
Controversy exists over whether aluminium has a role in the aetiology of Alzheimer's disease. Alzheimer's disease is neuropathologically characterized by the occurrence of a minimum density of neurofibrillary tangles and neuritic plaques in the hippocampus and the association cortex of the brain. The purported association of aluminium with Alzheimer's disease is based on: (1) the experimental induction of fibrillary changes in the neurons of animals by the injection of aluminium salts into brain tissue; (2) reported detection of aluminium in neuritic plaques and tangle-bearing neurons; (3) epidemiological studies linking aluminium levels in the environment, notably water supplies, with an increased prevalence of dementia; and (4) a reported decrease in the rate of disease progression following the administration of desferroxamine, an aluminium chelator, to clinically diagnosed sufferers of Alzheimer's disease. Here we use nuclear microscopy, a new analytical technique involving million-volt nuclear particles, to identify and analyse plaques in postmortem tissue from patients with Alzheimer's disease without using chemical staining techniques and fail to demonstrate the presence of aluminium in plaque cores in untreated tissue. 相似文献
42.
Production of poly-unsaturated ruminant body fats 总被引:1,自引:0,他引:1
43.
44.
Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities 总被引:1,自引:0,他引:1
Stegmeier F Rape M Draviam VM Nalepa G Sowa ME Ang XL McDonald ER Li MZ Hannon GJ Sorger PK Kirschner MW Harper JW Elledge SJ 《Nature》2007,446(7138):876-881
The spindle checkpoint prevents chromosome mis-segregation by delaying sister chromatid separation until all chromosomes have achieved bipolar attachment to the mitotic spindle. Its operation is essential for accurate chromosome segregation, whereas its dysregulation can contribute to birth defects and tumorigenesis. The target of the spindle checkpoint is the anaphase-promoting complex (APC), a ubiquitin ligase that promotes sister chromatid separation and progression to anaphase. Using a short hairpin RNA screen targeting components of the ubiquitin-proteasome pathway in human cells, we identified the deubiquitinating enzyme USP44 (ubiquitin-specific protease 44) as a critical regulator of the spindle checkpoint. USP44 is not required for the initial recognition of unattached kinetochores and the subsequent recruitment of checkpoint components. Instead, it prevents the premature activation of the APC by stabilizing the APC-inhibitory Mad2-Cdc20 complex. USP44 deubiquitinates the APC coactivator Cdc20 both in vitro and in vivo, and thereby directly counteracts the APC-driven disassembly of Mad2-Cdc20 complexes (discussed in an accompanying paper). Our findings suggest that a dynamic balance of ubiquitination by the APC and deubiquitination by USP44 contributes to the generation of the switch-like transition controlling anaphase entry, analogous to the way that phosphorylation and dephosphorylation of Cdk1 by Wee1 and Cdc25 controls entry into mitosis. 相似文献
45.
Friesen TL Stukenbrock EH Liu Z Meinhardt S Ling H Faris JD Rasmussen JB Solomon PS McDonald BA Oliver RP 《Nature genetics》2006,38(8):953-956
New diseases of humans, animals and plants emerge regularly. Enhanced virulence on a new host can be facilitated by the acquisition of novel virulence factors. Interspecific gene transfer is known to be a source of such virulence factors in bacterial pathogens (often manifested as pathogenicity islands in the recipient organism) and it has been speculated that interspecific transfer of virulence factors may occur in fungal pathogens. Until now, no direct support has been available for this hypothesis. Here we present evidence that a gene encoding a critical virulence factor was transferred from one species of fungal pathogen to another. This gene transfer probably occurred just before 1941, creating a pathogen population with significantly enhanced virulence and leading to the emergence of a new damaging disease of wheat. 相似文献
46.
Jaeger E Webb E Howarth K Carvajal-Carmona L Rowan A Broderick P Walther A Spain S Pittman A Kemp Z Sullivan K Heinimann K Lubbe S Domingo E Barclay E Martin L Gorman M Chandler I Vijayakrishnan J Wood W Papaemmanuil E Penegar S Qureshi M;CORGI Consortium Farrington S Tenesa A Cazier JB Kerr D Gray R Peto J Dunlop M Campbell H Thomas H Houlston R Tomlinson I 《Nature genetics》2008,40(1):26-28
We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1. We hypothesized that the CRAC1 locus harbored low-penetrance variants that increased CRC risk in the general population. In a large series of colorectal cancer cases and controls, SNPs near GREM1 and SCG5 were strongly associated with increased CRC risk (for rs4779584, P = 4.44 x 10(-14)). 相似文献
47.
Yu TW Mochida GH Tischfield DJ Sgaier SK Flores-Sarnat L Sergi CM Topçu M McDonald MT Barry BJ Felie JM Sunu C Dobyns WB Folkerth RD Barkovich AJ Walsh CA 《Nature genetics》2010,42(11):1015-1020
Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair. We describe a syndrome of congenital microcephaly and diverse defects in cerebral cortical architecture. Genome-wide linkage analysis in two families identified a 7.5-Mb locus on chromosome 19q13.12 containing 148 genes. Targeted high throughput sequence analysis of linked genes in each family yielded > 4,000 DNA variants and implicated a single gene, WDR62, as harboring potentially deleterious changes. We subsequently identified additional WDR62 mutations in four other families. Magnetic resonance imaging and postmortem brain analysis supports important roles for WDR62 in the proliferation and migration of neuronal precursors. WDR62 is a WD40 repeat-containing protein expressed in neuronal precursors as well as in postmitotic neurons in the developing brain and localizes to the spindle poles of dividing cells. The diverse phenotypes of WDR62 suggest it has central roles in many aspects of cerebral cortical development. 相似文献
48.
New protein fold revealed by a 2.3-A resolution crystal structure of nerve growth factor 总被引:34,自引:0,他引:34
N Q McDonald R Lapatto J Murray-Rust J Gunning A Wlodawer T L Blundell 《Nature》1991,354(6352):411-414
Nerve growth factor (NGF) is a member of an expanding family of neurotrophic factors (including brain-derived neurotrophic factor and the neurotrophins) that control the development and survival of certain neuronal populations both in the peripheral and in the central nervous systems. Its biological effects are mediated by a high-affinity ligand-receptor interaction and a tyrosine kinase signalling pathway. A potential use for NGF and its relatives in the treatment of neurological disorders such as Alzheimer's disease and Parkinson's disease requires an understanding of the structure-function relationships of NGF. NGF is a dimeric molecule, with 118 amino acids per protomer. We report the crystal structure of the murine NGF dimer at 2.3-A resolution, which reveals a novel protomer structure consisting of three antiparallel pairs of beta strands, together forming a flat surface. Two subunits associate through this surface, thus burying a total of 2,332 A. Four loop regions, which contain many of the variable residues observed between different NGF-related molecules, may determine the different receptor specificities. A clustering of positively charged side chains may provide a complementary interaction with the acidic low-affinity NGF receptor. The structure provides a model for rational design of analogues of NGF and its relatives and for testing the NGF-receptor recognition determinants critical for signal transduction. 相似文献
49.
R. H. Davis J. McDonald G. A. Kyriazis H. P. Schneider 《Cellular and molecular life sciences : CMLS》1973,29(10):1242-1242
Résumé Le % de distribution des cellules de fluide péritonéal d'une femelle adulte de singe rhésus fut enregistré dans des échantillons de fluide cytologique extraits par la paratomie. Les données sond comparées à celles qui ont obtenues précédemment chez la femme. 相似文献
50.
Pattern of remyelination in the CNS 总被引:3,自引:0,他引:3