全文获取类型
收费全文 | 100篇 |
免费 | 1篇 |
专业分类
系统科学 | 2篇 |
理论与方法论 | 3篇 |
现状及发展 | 32篇 |
研究方法 | 23篇 |
综合类 | 35篇 |
自然研究 | 6篇 |
出版年
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2012年 | 12篇 |
2011年 | 15篇 |
2010年 | 7篇 |
2008年 | 6篇 |
2007年 | 4篇 |
2006年 | 2篇 |
2005年 | 3篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2000年 | 2篇 |
1992年 | 1篇 |
1987年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1972年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有101条查询结果,搜索用时 15 毫秒
51.
52.
Hundreds of variants clustered in genomic loci and biological pathways affect human height 总被引:2,自引:0,他引:2
Lango Allen H Estrada K Lettre G Berndt SI Weedon MN Rivadeneira F Willer CJ Jackson AU Vedantam S Raychaudhuri S Ferreira T Wood AR Weyant RJ Segrè AV Speliotes EK Wheeler E Soranzo N Park JH Yang J Gudbjartsson D Heard-Costa NL Randall JC Qi L Vernon Smith A Mägi R Pastinen T Liang L Heid IM Luan J Thorleifsson G Winkler TW Goddard ME Sin Lo K Palmer C Workalemahu T Aulchenko YS Johansson A Zillikens MC Feitosa MF Esko T Johnson T Ketkar S Kraft P Mangino M Prokopenko I Absher D Albrecht E 《Nature》2010,467(7317):832-838
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P?0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways. 相似文献
53.
O'Sullivan JN Bronner MP Brentnall TA Finley JC Shen WT Emerson S Emond MJ Gollahon KA Moskovitz AH Crispin DA Potter JD Rabinovitch PS 《Nature genetics》2002,32(2):280-284
Ulcerative colitis, a chronic inflammatory disease of the colon, is associated with a high risk of colorectal carcinoma that is thought to develop through genomic instability. We considered that the rapid cell turnover and oxidative injury observed in ulcerative colitis might accelerate telomere shortening, thereby increasing the potential of chromosomal ends to fuse, resulting in cycles of chromatin bridge breakage and fusion and chromosomal instability associated with tumor cell progression. Here we have used quantitative fluorescence in situ hybridization to compare chromosomal aberrations and telomere shortening in non-dysplastic mucosa taken from individuals affected by ulcerative colitis, either with (UC progressors) or without (UC non-progressors) dysplasia or cancer. Losses, but not gains, of chromosomal arms and centromeres are highly correlated with telomere shortening. Chromosomal losses are greater and telomeres are shorter in biopsy samples from UC progressors than in those from UC non-progressors or control individuals without ulcerative colitis. A mechanistic link between telomere shortening and chromosomal instability is supported by a higher frequency of anaphase bridges--an intermediate in the breakage and fusion of chromatin bridges--in UC progressors than in UC non-progressors or control individuals. Our study shows that telomere length is correlated with chromosomal instability in a precursor of human cancer. 相似文献
54.
Effect of immune and normal RNA on the immunological response induced by rat red blood cells in mice
J. C. Morini M. V. Londner María Teresa Font S. L. Rabasa 《Cellular and molecular life sciences : CMLS》1969,25(6):640-641
Resumen Se inmunizaron ratones BALB con glóbulos rojos de ratas de una línea endocriada. A estos ratones se les extrajo el ARN del bazo y se inyectó a otro grupo de animales de la misma cepa. Además, se inyectó el ARN proveniente de bazo de ratón normal a un segundo grupo de animales. Cinco días después de la inyección del ARN normal e inmune, ambos grupos, y un tercero, testigo, recibieron una inyección de glóbulos rojos de rata. 相似文献
55.
Verjovski-Almeida S DeMarco R Martins EA Guimarães PE Ojopi EP Paquola AC Piazza JP Nishiyama MY Kitajima JP Adamson RE Ashton PD Bonaldo MF Coulson PS Dillon GP Farias LP Gregorio SP Ho PL Leite RA Malaquias LC Marques RC Miyasato PA Nascimento AL Ohlweiler FP Reis EM Ribeiro MA Sá RG Stukart GC Soares MB Gargioni C Kawano T Rodrigues V Madeira AM Wilson RA Menck CF Setubal JC Leite LC Dias-Neto E 《Nature genetics》2003,35(2):148-157
Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets. 相似文献
56.
A progeroid syndrome in mice is caused by defects in A-type lamins 总被引:21,自引:0,他引:21
Numerous studies of the underlying causes of ageing have been attempted by examining diseases associated with premature ageing, such as Werner's syndrome and Hutchinson-Gilford progeria syndrome (HGPS). HGPS is a rare genetic disorder resulting in phenotypes suggestive of accelerated ageing, including shortened stature, craniofacial disproportion, very thin skin, alopecia and osteoporosis, with death in the early teens predominantly due to atherosclerosis. However, recent reports suggest that developmental abnormalities may also be important in HGPS. Here we describe the derivation of mice carrying an autosomal recessive mutation in the lamin A gene (Lmna) encoding A-type lamins, major components of the nuclear lamina. Homozygous mice display defects consistent with HGPS, including a marked reduction in growth rate and death by 4 weeks of age. Pathologies in bone, muscle and skin are also consistent with progeria. The Lmna mutation resulted in nuclear morphology defects and decreased lifespan of homozygous fibroblasts, suggesting premature cell death. Here we present a mouse model for progeria that may elucidate mechanisms of ageing and development in certain tissue types, especially those developing from the mesenchymal cell lineage. 相似文献
57.
Summary The salivary secretion ofRhodnius prolixus inhibits both ADP and collagen induced platelet aggregation in human platelet-rich plasma. Fractionation studies show that at least 3 different inhibitors are present inRhodnius saliva. 相似文献
58.
The outbreak of Dutch elm disease in the 1970s ravaged European elm populations, killing more than 25 million trees in Britain alone; the greatest impact was on Ulmus procera, otherwise known as the English elm. Here we use molecular and historical information to show that this elm derives from a single clone that the Romans transported from Italy to the Iberian peninsula, and from there to Britain, for the purpose of supporting and training vines. Its highly efficient vegetative reproduction and its inability to set seeds have preserved this clone unaltered for 2,000 years as the core of the English elm population--and the preponderance of this susceptible variety may have favoured a rapid spread of the disease. 相似文献
59.
North TE Goessling W Walkley CR Lengerke C Kopani KR Lord AM Weber GJ Bowman TV Jang IH Grosser T Fitzgerald GA Daley GQ Orkin SH Zon LI 《Nature》2007,447(7147):1007-1011
60.
Jadwiga Jabłońska Magda Dubińska-Magiera Teresa Jagla Krzysztof Jagla Małgorzata Daczewska 《Cellular and molecular life sciences : CMLS》2018,75(23):4341-4356
The Drosophila Hsp67Bc gene encodes a protein belonging to the small heat-shock protein (sHSP) family, identified as the nearest functional ortholog of human HSPB8. The most prominent activity of sHSPs is preventing the irreversible aggregation of various non-native polypeptides. Moreover, they are involved in processes such as development, aging, maintenance of the cytoskeletal architecture and autophagy. In larval muscles Hsp67Bc localizes to the Z- and A-bands, which suggests its role as part of the conserved chaperone complex required for Z-disk maintenance. In addition, Hsp67Bc is present at neuromuscular junctions (NMJs), which implies its involvement in the maintenance of NMJ structure. Here, we report the effects of muscle-target overexpression of Drosophila Hsp67Bc hot-spot variants Hsp67BcR126E and Hsp67BcR126N mimicking pathogenic variants of human HSPB8. Depending on the substitutions, we observed a different impact on muscle structure and performance. Expression of Hsp67BcR126E affects larval motility, which may be caused by impairment of mitochondrial respiratory function and/or by NMJ abnormalities manifested by a decrease in the number of synaptic boutons. In contrast, Hsp67BcR126N appears to be an aggregate-prone variant, as reflected in excessive accumulation of mutant proteins and the formation of large aggregates with a lesser impact on muscle structure and performance compared to the Hsp67BcR126E variant. 相似文献