全文获取类型
收费全文 | 400篇 |
免费 | 1篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 6篇 |
丛书文集 | 1篇 |
教育与普及 | 1篇 |
理论与方法论 | 8篇 |
现状及发展 | 66篇 |
研究方法 | 60篇 |
综合类 | 231篇 |
自然研究 | 29篇 |
出版年
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 6篇 |
2014年 | 3篇 |
2013年 | 7篇 |
2012年 | 37篇 |
2011年 | 69篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 24篇 |
2007年 | 32篇 |
2006年 | 34篇 |
2005年 | 33篇 |
2004年 | 30篇 |
2003年 | 19篇 |
2002年 | 22篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1982年 | 1篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1966年 | 4篇 |
1965年 | 4篇 |
1961年 | 1篇 |
1956年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有402条查询结果,搜索用时 197 毫秒
1.
Recombination and linkage disequilibrium in Arabidopsis thaliana 总被引:4,自引:0,他引:4
Kim S Plagnol V Hu TT Toomajian C Clark RM Ossowski S Ecker JR Weigel D Nordborg M 《Nature genetics》2007,39(9):1151-1155
Linkage disequilibrium (LD) is a major aspect of the organization of genetic variation in natural populations. Here we describe the genome-wide pattern of LD in a sample of 19 Arabidopsis thaliana accessions using 341,602 non-singleton SNPs. LD decays within 10 kb on average, considerably faster than previously estimated. Tag SNP selection algorithms and 'hide-the-SNP' simulations suggest that genome-wide association mapping will require only 40%-50% of the observed SNPs, a reduction similar to estimates in a sample of African Americans. An Affymetrix genotyping array containing 250,000 SNPs has been designed based on these results; we demonstrate that it should have more than adequate coverage for genome-wide association mapping. The extent of LD is highly variable, and we find clear evidence of recombination hotspots, which seem to occur preferentially in intergenic regions. LD also reflects the action of selection, and it is more extensive between nonsynonymous polymorphisms than between synonymous polymorphisms. 相似文献
2.
Risheg H Graham JM Clark RD Rogers RC Opitz JM Moeschler JB Peiffer AP May M Joseph SM Jones JR Stevenson RE Schwartz CE Friez MJ 《Nature genetics》2007,39(4):451-453
Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex. 相似文献
3.
Lindahl E Nyman U Melles E Sigmundsson K Ståhlberg M Wahren J Obrink B Shafqat J Joseph B Jörnvall H 《Cellular and molecular life sciences : CMLS》2007,64(4):479-486
Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is
internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide,
we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport
into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at
4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive
mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated
binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components
to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence
of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that
of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action.
Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006 相似文献
4.
Schlesinger Y Straussman R Keshet I Farkash S Hecht M Zimmerman J Eden E Yakhini Z Ben-Shushan E Reubinoff BE Bergman Y Simon I Cedar H 《Nature genetics》2007,39(2):232-236
Many genes associated with CpG islands undergo de novo methylation in cancer. Studies have suggested that the pattern of this modification may be partially determined by an instructive mechanism that recognizes specifically marked regions of the genome. Using chromatin immunoprecipitation analysis, here we show that genes methylated in cancer cells are specifically packaged with nucleosomes containing histone H3 trimethylated on Lys27. This chromatin mark is established on these unmethylated CpG island genes early in development and then maintained in differentiated cell types by the presence of an EZH2-containing Polycomb complex. In cancer cells, as opposed to normal cells, the presence of this complex brings about the recruitment of DNA methyl transferases, leading to de novo methylation. These results suggest that tumor-specific targeting of de novo methylation is pre-programmed by an established epigenetic system that normally has a role in marking embryonic genes for repression. 相似文献
5.
6.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
7.
这本专著总结了作者多年来最重要的研究成果。研究表明,人的大脑皮层具有获得驱动力的独特能力.正是这种能力创造了人类社会,并促使人类社会不断进化。作者认为,人类社会目前还处于反复实验的发展阶段,但其最终必将由现在的不可知状态逐渐过渡到理性指导的平衡状态。通过对获得性驱动力的特殊分析及以前曾认为不可知的脑机理的发现,作者对社会生活的发展及艺术、科学的起源给出了合理的生理学解释。本书的目的是要论证即使在脑及其自我的关系中,自然规律仍然是简单的,而不是不可知的。 相似文献
8.
9.
Luiz A. Rocha Joseph D. DiBattista Tane H. Sinclair-Taylor Michael L. Berumen 《Journal of Natural History》2020,54(15-16):1019-1023
ABSTRACT Here we document three cases of mimicry in coral reef fishes not previously reported in the literature involving two groupers (Epinephelus leucogrammicus and Plectropomus marisrubri) and a soapfish (Diploprion drachi) as mimics, and two wrasses (Larabicus quadrilineatus and Cheilinus quinquecinctus) and a blenny (Meiacanthus nigrolineatus) as models. All three cases are of aggressive mimicry, with a predatory species mimicking a harmless one, and in one of the cases, the mimicry is also Müllerian, where both the predator and harmless species are unpalatable. 相似文献
10.
Milne JC Lambert PD Schenk S Carney DP Smith JJ Gagne DJ Jin L Boss O Perni RB Vu CB Bemis JE Xie R Disch JS Ng PY Nunes JJ Lynch AV Yang H Galonek H Israelian K Choy W Iffland A Lavu S Medvedik O Sinclair DA Olefsky JM Jirousek MR Elliott PJ Westphal CH 《Nature》2007,450(7170):712-716
Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes. 相似文献