全文获取类型
收费全文 | 154篇 |
免费 | 0篇 |
专业分类
丛书文集 | 1篇 |
教育与普及 | 4篇 |
现状及发展 | 5篇 |
研究方法 | 29篇 |
综合类 | 115篇 |
出版年
2012年 | 16篇 |
2011年 | 20篇 |
2010年 | 2篇 |
2008年 | 11篇 |
2007年 | 8篇 |
2006年 | 6篇 |
2005年 | 10篇 |
2004年 | 9篇 |
2003年 | 6篇 |
2002年 | 9篇 |
2001年 | 3篇 |
2000年 | 9篇 |
1999年 | 2篇 |
1997年 | 1篇 |
1993年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1984年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1971年 | 3篇 |
1970年 | 7篇 |
1959年 | 2篇 |
1958年 | 6篇 |
1957年 | 5篇 |
1956年 | 2篇 |
1955年 | 1篇 |
1954年 | 3篇 |
1948年 | 4篇 |
1946年 | 1篇 |
排序方式: 共有154条查询结果,搜索用时 296 毫秒
1.
2.
RNA polymerase is poised for activation across the genome 总被引:2,自引:0,他引:2
Muse GW Gilchrist DA Nechaev S Shah R Parker JS Grissom SF Zeitlinger J Adelman K 《Nature genetics》2007,39(12):1507-1511
3.
Shimamura T Shiroishi M Weyand S Tsujimoto H Winter G Katritch V Abagyan R Cherezov V Liu W Han GW Kobayashi T Stevens RC Iwata S 《Nature》2011,475(7354):65-70
The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H(1) receptor (H(1)R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H(1)R complex with doxepin, a first-generation H(1)R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp?428(6.48), a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H(1)R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys?191(5.39) and/or Lys?179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R. 相似文献
4.
5.
Lissauer JJ Fabrycky DC Ford EB Borucki WJ Fressin F Marcy GW Orosz JA Rowe JF Torres G Welsh WF Batalha NM Bryson ST Buchhave LA Caldwell DA Carter JA Charbonneau D Christiansen JL Cochran WD Desert JM Dunham EW Fanelli MN Fortney JJ Gautier TN Geary JC Gilliland RL Haas MR Hall JR Holman MJ Koch DG Latham DW Lopez E McCauliff S Miller N Morehead RC Quintana EV Ragozzine D Sasselov D Short DR Steffen JH 《Nature》2011,470(7332):53-58
When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47?days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation. 相似文献
6.
Yang J Ferreira T Morris AP Medland SE;Genetic Investigation of ANthropometric Traits 《Nature genetics》2012,44(4):369-75, S1-3
We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium. 相似文献
7.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of
calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded
in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels
is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and
interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current
state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and
internalization of this important ion channel family. 相似文献
8.
Burdon KP Macgregor S Hewitt AW Sharma S Chidlow G Mills RA Danoy P Casson R Viswanathan AC Liu JZ Landers J Henders AK Wood J Souzeau E Crawford A Leo P Wang JJ Rochtchina E Nyholt DR Martin NG Montgomery GW Mitchell P Brown MA Mackey DA Craig JE 《Nature genetics》2011,43(6):574-578
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. 相似文献
9.
Santen GW Aten E Sun Y Almomani R Gilissen C Nielsen M Kant SG Snoeck IN Peeters EA Hilhorst-Hofstee Y Wessels MW den Hollander NS Ruivenkamp CA van Ommen GJ Breuning MH den Dunnen JT van Haeringen A Kriek M 《Nature genetics》2012,44(4):379-380
We identified de novo truncating mutations in ARID1B in three individuals with Coffin-Siris syndrome (CSS) by exome sequencing. Array-based copy-number variation (CNV) analysis in 2,000 individuals with intellectual disability revealed deletions encompassing ARID1B in 3 subjects with phenotypes partially overlapping that of CSS. Taken together with published data, these results indicate that haploinsufficiency of the ARID1B gene, which encodes an epigenetic modifier of chromatin structure, is an important cause of CSS and is potentially a common cause of intellectual disability and speech impairment. 相似文献
10.
Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex 总被引:36,自引:0,他引:36
Do new synapses form in the adult cortex to support experience-dependent plasticity? To address this question, we repeatedly imaged individual pyramidal neurons in the mouse barrel cortex over periods of weeks. We found that, although dendritic structure is stable, some spines appear and disappear. Spine lifetimes vary greatly: stable spines, about 50% of the population, persist for at least a month, whereas the remainder are present for a few days or less. Serial-section electron microscopy of imaged dendritic segments revealed retrospectively that spine sprouting and retraction are associated with synapse formation and elimination. Experience-dependent plasticity of cortical receptive fields was accompanied by increased synapse turnover. Our measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits. 相似文献