全文获取类型
收费全文 | 150篇 |
免费 | 1篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 3篇 |
理论与方法论 | 5篇 |
现状及发展 | 25篇 |
研究方法 | 27篇 |
综合类 | 88篇 |
自然研究 | 6篇 |
出版年
2021年 | 1篇 |
2019年 | 2篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 1篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2012年 | 13篇 |
2011年 | 19篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2008年 | 10篇 |
2007年 | 9篇 |
2006年 | 14篇 |
2005年 | 11篇 |
2004年 | 16篇 |
2003年 | 5篇 |
2002年 | 15篇 |
2000年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1974年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有154条查询结果,搜索用时 15 毫秒
51.
Tenesa A Farrington SM Prendergast JG Porteous ME Walker M Haq N Barnetson RA Theodoratou E Cetnarskyj R Cartwright N Semple C Clark AJ Reid FJ Smith LA Kavoussanakis K Koessler T Pharoah PD Buch S Schafmayer C Tepel J Schreiber S Völzke H Schmidt CO Hampe J Chang-Claude J Hoffmeister M Brenner H Wilkening S Canzian F Capella G Moreno V Deary IJ Starr JM Tomlinson IP Kemp Z Howarth K Carvajal-Carmona L Webb E Broderick P Vijayakrishnan J Houlston RS Rennert G Ballinger D Rozek L Gruber SB 《Nature genetics》2008,40(5):631-637
In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology. 相似文献
52.
A phenylalanine in DGAT is a key determinant of oil content and composition in maize 总被引:9,自引:0,他引:9
Zheng P Allen WB Roesler K Williams ME Zhang S Li J Glassman K Ranch J Nubel D Solawetz W Bhattramakki D Llaca V Deschamps S Zhong GY Tarczynski MC Shen B 《Nature genetics》2008,40(3):367-372
Plant oil is an important renewable resource for biodiesel production and for dietary consumption by humans and livestock. Through genetic mapping of the oil trait in plants, studies have reported multiple quantitative trait loci (QTLs) with small effects, but the molecular basis of oil QTLs remains largely unknown. Here we show that a high-oil QTL (qHO6) affecting maize seed oil and oleic-acid contents encodes an acyl-CoA:diacylglycerol acyltransferase (DGAT1-2), which catalyzes the final step of oil synthesis. We further show that a phenylalanine insertion in DGAT1-2 at position 469 (F469) is responsible for the increased oil and oleic-acid contents. The DGAT1-2 allele with F469 is ancestral, whereas the allele without F469 is a more recent mutant selected by domestication or breeding. Ectopic expression of the high-oil DGAT1-2 allele increases oil and oleic-acid contents by up to 41% and 107%, respectively. This work provides insights into the molecular basis of natural variation of oil and oleic-acid contents in plants and highlights DGAT as a promising target for increasing oil and oleic-acid contents in other crops. 相似文献
53.
Caledophora gen. nov. is described based on two new species from New Caledonia, Caledophora irwini sp.nov. and Caledophora webbi sp.nov. This genus is similar to some genera from New Zealand, but can be differentiated from them by the combination of hypopygium not being expanded dorsoventrally, frons setation 4-4-4, light body colour and wing without vein R2+3. Its phylogenetic position is inferred to be within the Bothroprosopa-group of genera.
www.zoobank.org/urn:lsid:zoobank.org:pub:F6263E01-F2EF-4204-89D6-55BFD7A7AC00 相似文献
54.
Polar organisms have adapted their seasonal cycles to the dynamic interface between ice and water. This interface ranges from the micrometre-sized brine channels within sea ice to the planetary-scale advance and retreat of sea ice. Polar marine ecosystems are particularly sensitive to climate change because small temperature differences can have large effects on the extent and thickness of sea ice. Little is known about the interactions between large, long-lived organisms and their planktonic food supply. Disentangling the effects of human exploitation of upper trophic levels from basin-wide, decade-scale climate cycles to identify long-term, global trends is a daunting challenge facing polar bio-oceanography. 相似文献
55.
Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice 总被引:56,自引:0,他引:56
Zhu S Stavrovskaya IG Drozda M Kim BY Ona V Li M Sarang S Liu AS Hartley DM Wu DC Gullans S Ferrante RJ Przedborski S Kristal BS Friedlander RM 《Nature》2002,417(6884):74-78
Minocycline mediates neuroprotection in experimental models of neurodegeneration. It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although minocycline does not directly inhibit these enzymes, the effects may result from interference with upstream mechanisms resulting in their secondary activation. Because the above-mentioned factors are important in amyotrophic lateral sclerosis (ALS), we tested minocycline in mice with ALS. Here we report that minocycline delays disease onset and extends survival in ALS mice. Given the broad efficacy of minocycline, understanding its mechanisms of action is of great importance. We find that minocycline inhibits mitochondrial permeability-transition-mediated cytochrome c release. Minocycline-mediated inhibition of cytochrome c release is demonstrated in vivo, in cells, and in isolated mitochondria. Understanding the mechanism of action of minocycline will assist in the development and testing of more powerful and effective analogues. Because of the safety record of minocycline, and its ability to penetrate the blood-brain barrier, this drug may be a novel therapy for ALS. 相似文献
56.
57.
Hatching chronology of Blue Grouse ( Dendragapus obscurus ) in northeastern Oregon was determined from 431 immatures examined from 1981 to 1985. Young hatched from 1 May through 8 July; median hatching dates for the five years ranged from 27 May to 5 June. Peak hatching in Oregon occurred from one to four weeks earlier than in most portions of the range of Blue Grouse but were similar to north central Washington and Idaho. Variations in hatching dates possibly were related to rainfall. 相似文献
58.
59.
Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter 总被引:2,自引:0,他引:2
Baughman JM Perocchi F Girgis HS Plovanich M Belcher-Timme CA Sancak Y Bao XR Strittmatter L Goldberger O Bogorad RL Koteliansky V Mootha VK 《Nature》2011,476(7360):341-345
Mitochondria from diverse organisms are capable of transporting large amounts of Ca(2+) via a ruthenium-red-sensitive, membrane-potential-dependent mechanism called the uniporter. Although the uniporter's biophysical properties have been studied extensively, its molecular composition remains elusive. We recently used comparative proteomics to identify MICU1 (also known as CBARA1), an EF-hand-containing protein that serves as a putative regulator of the uniporter. Here, we use whole-genome phylogenetic profiling, genome-wide RNA co-expression analysis and organelle-wide protein coexpression analysis to predict proteins functionally related to MICU1. All three methods converge on a novel predicted transmembrane protein, CCDC109A, that we now call 'mitochondrial calcium uniporter' (MCU). MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU in cultured cells or in vivo in mouse liver severely abrogates mitochondrial Ca(2+) uptake, whereas mitochondrial respiration and membrane potential remain fully intact. MCU has two predicted transmembrane helices, which are separated by a highly conserved linker facing the intermembrane space. Acidic residues in this linker are required for its full activity. However, an S259A point mutation retains function but confers resistance to Ru360, the most potent inhibitor of the uniporter. Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca(2+) uniporter. 相似文献
60.
Ressler KJ Mercer KB Bradley B Jovanovic T Mahan A Kerley K Norrholm SD Kilaru V Smith AK Myers AJ Ramirez M Engel A Hammack SE Toufexis D Braas KM Binder EB May V 《Nature》2011,470(7335):492-497
Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to broadly regulate the cellular stress response. In contrast, it is unclear if the PACAP-PAC1 receptor pathway has a role in human psychological stress responses, such as post-traumatic stress disorder (PTSD). Here we find, in heavily traumatized subjects, a sex-specific association of PACAP blood levels with fear physiology, PTSD diagnosis and symptoms in females. We examined 44 single nucleotide polymorphisms (SNPs) spanning the PACAP (encoded by ADCYAP1) and PAC1 (encoded by ADCYAP1R1) genes, demonstrating a sex-specific association with PTSD. A single SNP in a putative oestrogen response element within ADCYAP1R1, rs2267735, predicts PTSD diagnosis and symptoms in females only. This SNP also associates with fear discrimination and with ADCYAP1R1 messenger RNA expression in human brain. Methylation of ADCYAP1R1 in peripheral blood is also associated with PTSD. Complementing these human data, ADCYAP1R1 mRNA is induced with fear conditioning or oestrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via oestrogen regulation of ADCYAP1R1. PACAP levels and ADCYAP1R1 SNPs may serve as useful biomarkers to further our mechanistic understanding of PTSD. 相似文献