全文获取类型
收费全文 | 259篇 |
免费 | 0篇 |
专业分类
理论与方法论 | 1篇 |
现状及发展 | 40篇 |
研究方法 | 30篇 |
综合类 | 183篇 |
自然研究 | 5篇 |
出版年
2016年 | 1篇 |
2012年 | 14篇 |
2011年 | 12篇 |
2010年 | 2篇 |
2008年 | 17篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 16篇 |
2004年 | 5篇 |
2003年 | 7篇 |
2002年 | 14篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 6篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 7篇 |
1970年 | 11篇 |
1969年 | 10篇 |
1968年 | 2篇 |
1967年 | 13篇 |
1966年 | 8篇 |
1965年 | 5篇 |
1958年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有259条查询结果,搜索用时 546 毫秒
151.
152.
153.
S Bowman D Lawson D Basham D Brown T Chillingworth C M Churcher A Craig R M Davies K Devlin T Feltwell S Gentles R Gwilliam N Hamlin D Harris S Holroyd T Hornsby P Horrocks K Jagels B Jassal S Kyes J McLean S Moule K Mungall L Murphy K Oliver M A Quail M A Rajandream S Rutter J Skelton R Squares S Squares J E Sulston S Whitehead J R Woodward C Newbold B G Barrell 《Nature》1999,400(6744):532-538
Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes. 相似文献
154.
Smith UM Consugar M Tee LJ McKee BM Maina EN Whelan S Morgan NV Goranson E Gissen P Lilliquist S Aligianis IA Ward CJ Pasha S Punyashthiti R Malik Sharif S Batman PA Bennett CP Woods CG McKeown C Bucourt M Miller CA Cox P Algazali L Trembath RC Torres VE Attie-Bitach T Kelly DA Maher ER Gattone VH Harris PC Johnson CA 《Nature genetics》2006,38(2):191-196
Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin. 相似文献
155.
The yak genome and adaptation to life at high altitude 总被引:8,自引:0,他引:8
Qiu Q Zhang G Ma T Qian W Wang J Ye Z Cao C Hu Q Kim J Larkin DM Auvil L Capitanu B Ma J Lewin HA Qian X Lang Y Zhou R Wang L Wang K Xia J Liao S Pan S Lu X Hou H Wang Y Zang X Yin Y Ma H Zhang J Wang Z Zhang Y Zhang D Yonezawa T Hasegawa M Zhong Y Liu W Zhang Y Huang Z Zhang S Long R Yang H Wang J Lenstra JA Cooper DN Wu Y Wang J Shi P Wang J Liu J 《Nature genetics》2012,44(8):946-949
Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans. 相似文献
156.
Aragonés J Schneider M Van Geyte K Fraisl P Dresselaers T Mazzone M Dirkx R Zacchigna S Lemieux H Jeoung NH Lambrechts D Bishop T Lafuste P Diez-Juan A Harten SK Van Noten P De Bock K Willam C Tjwa M Grosfeld A Navet R Moons L Vandendriessche T Deroose C Wijeyekoon B Nuyts J Jordan B Silasi-Mansat R Lupu F Dewerchin M Pugh C Salmon P Mortelmans L Gallez B Gorus F Buyse J Sluse F Harris RA Gnaiger E Hespel P Van Hecke P Schuit F Van Veldhoven P Ratcliffe P Baes M Maxwell P Carmeliet P 《Nature genetics》2008,40(2):170-180
HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress. 相似文献
157.
Aitman TJ Critser JK Cuppen E Dominiczak A Fernandez-Suarez XM Flint J Gauguier D Geurts AM Gould M Harris PC Holmdahl R Hubner N Izsvák Z Jacob HJ Kuramoto T Kwitek AE Marrone A Mashimo T Moreno C Mullins J Mullins L Olsson T Pravenec M Riley L Saar K Serikawa T Shull JD Szpirer C Twigger SN Voigt B Worley K 《Nature genetics》2008,40(5):516-522
The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. Genome-wide association studies in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains problematic. In the context of significant progress in rat genomic resources over the past decade, we outline achievements in rat gene discovery to date, show how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms. Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research. 相似文献
158.
New models of collaboration in genome-wide association studies: the Genetic Association Information Network 总被引:7,自引:0,他引:7
GAIN Collaborative Research Group Manolio TA Rodriguez LL Brooks L Abecasis G;Collaborative Association Study of Psoriasis Ballinger D Daly M Donnelly P Faraone SV;International Multi-Center ADHD Genetics Project Frazer K Gabriel S Gejman P;Molecular Genetics of Schizophrenia Collaboration Guttmacher A Harris EL Insel T Kelsoe JR;Bipolar Genome Study Lander E McCowin N Mailman MD Nabel E Ostell J Pugh E Sherry S 《Nature genetics》2007,39(9):1045-1051
The Genetic Association Information Network (GAIN) is a public-private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases. 相似文献
159.
Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning 总被引:19,自引:0,他引:19
Therapeutic cloning, whereby somatic cell nuclear transfer (SCNT) is used to generate patient-specific embryonic stem cells (ESCs) from blastocysts cloned by nuclear transfer (ntESCs), holds great promise for the treatment of many human diseases. ntESCs have been derived in mice and cattle, but thus far there are no credible reports of human ntESCs. Here we review the recent literature on nuclear reprogramming by SCNT, including studies of gene expression, DNA methylation, chromatin remodeling, genomic imprinting and X chromosome inactivation. Reprogramming of genes expressed in the inner cell mass, from which ntESCs are derived, seems to be highly efficient. Defects in the extraembryonic lineage are probably the major cause of the low success rate of reproductive cloning but are not expected to affect the derivation of ntESCs. We remain optimistic that human therapeutic cloning is achievable and that the derivation of patient-specific ntESC lines will have great potential for regenerative medicine. 相似文献
160.
Heid IM Jackson AU Randall JC Winkler TW Qi L Steinthorsdottir V Thorleifsson G Zillikens MC Speliotes EK Mägi R Workalemahu T White CC Bouatia-Naji N Harris TB Berndt SI Ingelsson E Willer CJ Weedon MN Luan J Vedantam S Esko T Kilpeläinen TO Kutalik Z Li S Monda KL Dixon AL Holmes CC Kaplan LM Liang L Min JL Moffatt MF Molony C Nicholson G Schadt EE Zondervan KT Feitosa MF Ferreira T Lango Allen H Weyant RJ Wheeler E Wood AR;MAGIC Estrada K Goddard ME Lettre G Mangino M Nyholt DR Purcell S 《Nature genetics》2010,42(11):949-960
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10?? to P = 1.8 × 10???) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10?3 to P = 1.2 × 10?13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. 相似文献