全文获取类型
收费全文 | 280篇 |
免费 | 0篇 |
专业分类
教育与普及 | 21篇 |
理论与方法论 | 3篇 |
现状及发展 | 11篇 |
研究方法 | 33篇 |
综合类 | 212篇 |
出版年
2012年 | 10篇 |
2011年 | 20篇 |
2010年 | 2篇 |
2009年 | 1篇 |
2008年 | 13篇 |
2007年 | 16篇 |
2006年 | 14篇 |
2005年 | 18篇 |
2004年 | 15篇 |
2003年 | 20篇 |
2002年 | 13篇 |
2001年 | 13篇 |
2000年 | 22篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1972年 | 1篇 |
1971年 | 7篇 |
1970年 | 12篇 |
1960年 | 2篇 |
1959年 | 4篇 |
1958年 | 9篇 |
1957年 | 6篇 |
1956年 | 6篇 |
1955年 | 4篇 |
1954年 | 4篇 |
1948年 | 12篇 |
排序方式: 共有280条查询结果,搜索用时 311 毫秒
11.
St Onge RP Mani R Oh J Proctor M Fung E Davis RW Nislow C Roth FP Giaever G 《Nature genetics》2007,39(2):199-206
Systematic genetic interaction studies have illuminated many cellular processes. Here we quantitatively examine genetic interactions among 26 Saccharomyces cerevisiae genes conferring resistance to the DNA-damaging agent methyl methanesulfonate (MMS), as determined by chemogenomic fitness profiling of pooled deletion strains. We constructed 650 double-deletion strains, corresponding to all pairings of these 26 deletions. The fitness of single- and double-deletion strains were measured in the presence and absence of MMS. Genetic interactions were defined by combining principles from both statistical and classical genetics. The resulting network predicts that the Mph1 helicase has a role in resolving homologous recombination-derived DNA intermediates that is similar to (but distinct from) that of the Sgs1 helicase. Our results emphasize the utility of small molecules and multifactorial deletion mutants in uncovering functional relationships and pathway order. 相似文献
12.
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants 总被引:2,自引:0,他引:2
Wellcome Trust Case Control Consortium;Australo-Anglo-American Spondylitis Consortium 《Nature genetics》2007,39(11):1329-1337
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases. 相似文献
13.
Steinbusch LK Schwenk RW Ouwens DM Diamant M Glatz JF Luiken JJ 《Cellular and molecular life sciences : CMLS》2011,68(15):2525-2538
Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose
transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored
in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well
as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly
affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized
at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate
uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences
in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved
in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both
GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking
components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development
of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy. 相似文献
14.
Pattern formation of biological structures involves organizing different types of cells into a spatial configuration. In this study, we investigate the physical basis of biological patterning of the Drosophila retina in vivo. We demonstrate that E- and N-cadherins mediate apical adhesion between retina epithelial cells. Differential expression of N-cadherin within a sub-group of retinal cells (cone cells) causes them to form an overall shape that minimizes their surface contact with surrounding cells. The cells within this group, in both normal and experimentally manipulated conditions, pack together in the same way as soap bubbles do. The shaping of the cone cell group and packing of its components precisely imitate the physical tendency for surfaces to be minimized. Thus, simple patterned expression of N-cadherin results in a complex spatial pattern of cells owing to cellular surface mechanics. 相似文献
15.
16.
17.
Speer RJ Garton WR Morgan JF Nicholls RW Goldberg L Parkinson WH Reeves EM Jones TJ Paxton HJ Shenton DB Wilson R 《Nature》1970,226(5242):249-250
Flash spectra of the total solar eclipse throughout all its phases have been obtained in the extreme ultraviolet for the first time. 相似文献
18.
Systematic screen for human disease genes in yeast 总被引:19,自引:0,他引:19
Steinmetz LM Scharfe C Deutschbauer AM Mokranjac D Herman ZS Jones T Chu AM Giaever G Prokisch H Oefner PJ Davis RW 《Nature genetics》2002,31(4):400-404
High similarity between yeast and human mitochondria allows functional genomic study of Saccharomyces cerevisiae to be used to identify human genes involved in disease. So far, 102 heritable disorders have been attributed to defects in a quarter of the known nuclear-encoded mitochondrial proteins in humans. Many mitochondrial diseases remain unexplained, however, in part because only 40-60% of the presumed 700-1,000 proteins involved in mitochondrial function and biogenesis have been identified. Here we apply a systematic functional screen using the pre-existing whole-genome pool of yeast deletion mutants to identify mitochondrial proteins. Three million measurements of strain fitness identified 466 genes whose deletions impaired mitochondrial respiration, of which 265 were new. Our approach gave higher selection than other systematic approaches, including fivefold greater selection than gene expression analysis. To apply these advantages to human disorders involving mitochondria, human orthologs were identified and linked to heritable diseases using genomic map positions. 相似文献
19.
Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms 总被引:39,自引:0,他引:39
Barouch LA Harrison RW Skaf MW Rosas GO Cappola TP Kobeissi ZA Hobai IA Lemmon CA Burnett AL O'Rourke B Rodriguez ER Huang PL Lima JA Berkowitz DE Hare JM 《Nature》2002,416(6878):337-339
Subcellular localization of nitric oxide (NO) synthases with effector molecules is an important regulatory mechanism for NO signalling. In the heart, NO inhibits L-type Ca2+ channels but stimulates sarcoplasmic reticulum (SR) Ca2+ release, leading to variable effects on myocardial contractility. Here we show that spatial confinement of specific NO synthase isoforms regulates this process. Endothelial NO synthase (NOS3) localizes to caveolae, where compartmentalization with beta-adrenergic receptors and L-type Ca2+ channels allows NO to inhibit beta-adrenergic-induced inotropy. Neuronal NO synthase (NOS1), however, is targeted to cardiac SR. NO stimulation of SR Ca2+ release via the ryanodine receptor (RyR) in vitro, suggests that NOS1 has an opposite, facilitative effect on contractility. We demonstrate that NOS1-deficient mice have suppressed inotropic response, whereas NOS3-deficient mice have enhanced contractility, owing to corresponding changes in SR Ca2+ release. Both NOS1-/- and NOS3-/- mice develop age-related hypertrophy, although only NOS3-/- mice are hypertensive. NOS1/3-/- double knockout mice have suppressed beta-adrenergic responses and an additive phenotype of marked ventricular remodelling. Thus, NOS1 and NOS3 mediate independent, and in some cases opposite, effects on cardiac structure and function. 相似文献
20.