全文获取类型
收费全文 | 964篇 |
免费 | 3篇 |
国内免费 | 4篇 |
专业分类
系统科学 | 7篇 |
丛书文集 | 1篇 |
教育与普及 | 4篇 |
理论与方法论 | 14篇 |
现状及发展 | 80篇 |
研究方法 | 193篇 |
综合类 | 607篇 |
自然研究 | 65篇 |
出版年
2020年 | 4篇 |
2018年 | 6篇 |
2017年 | 13篇 |
2016年 | 8篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 9篇 |
2012年 | 86篇 |
2011年 | 161篇 |
2010年 | 26篇 |
2009年 | 9篇 |
2008年 | 81篇 |
2007年 | 96篇 |
2006年 | 98篇 |
2005年 | 88篇 |
2004年 | 68篇 |
2003年 | 79篇 |
2002年 | 86篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 4篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有971条查询结果,搜索用时 953 毫秒
41.
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus 总被引:1,自引:0,他引:1
Zhu L Vranckx R Khau Van Kien P Lalande A Boisset N Mathieu F Wegman M Glancy L Gasc JM Brunotte F Bruneval P Wolf JE Michel JB Jeunemaitre X 《Nature genetics》2006,38(3):343-349
We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease. 相似文献
42.
High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi 总被引:1,自引:0,他引:1
Holt KE Parkhill J Mazzoni CJ Roumagnac P Weill FX Goodhead I Rance R Baker S Maskell DJ Wain J Dolecek C Achtman M Dougan G 《Nature genetics》2008,40(8):987-993
Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. We generated whole-genome sequences for 19 Typhi isolates using 454 (Roche) and Solexa (Illumina) technologies. Isolates, including the previously sequenced CT18 and Ty2 isolates, were selected to represent major nodes in the phylogenetic tree. Comparative analysis showed little evidence of purifying selection, antigenic variation or recombination between isolates. Rather, evolution in the Typhi population seems to be characterized by ongoing loss of gene function, consistent with a small effective population size. The lack of evidence for antigenic variation driven by immune selection is in contrast to strong adaptive selection for mutations conferring antibiotic resistance in Typhi. The observed patterns of genetic isolation and drift are consistent with the proposed key role of asymptomatic carriers of Typhi as the main reservoir of this pathogen, highlighting the need for identification and treatment of carriers. 相似文献
43.
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans 总被引:2,自引:0,他引:2
Kathiresan S Melander O Guiducci C Surti A Burtt NP Rieder MJ Cooper GM Roos C Voight BF Havulinna AS Wahlstrand B Hedner T Corella D Tai ES Ordovas JM Berglund G Vartiainen E Jousilahti P Hedblad B Taskinen MR Newton-Cheh C Salomaa V Peltonen L Groop L Altshuler DM Orho-Melander M 《Nature genetics》2008,40(2):189-197
44.
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes 总被引:1,自引:0,他引:1
Zeggini E Scott LJ Saxena R Voight BF Marchini JL Hu T de Bakker PI Abecasis GR Almgren P Andersen G Ardlie K Boström KB Bergman RN Bonnycastle LL Borch-Johnsen K Burtt NP Chen H Chines PS Daly MJ Deodhar P Ding CJ Doney AS Duren WL Elliott KS Erdos MR Frayling TM Freathy RM Gianniny L Grallert H Grarup N Groves CJ Guiducci C Hansen T Herder C Hitman GA Hughes TE Isomaa B Jackson AU Jørgensen T Kong A Kubalanza K Kuruvilla FG Kuusisto J Langenberg C Lango H Lauritzen T Li Y Lindgren CM 《Nature genetics》2008,40(5):638-645
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. 相似文献
45.
In this paper, we first extract factors from a monthly dataset of 130 macroeconomic and financial variables. These extracted factors are then used to construct a factor‐augmented qualitative vector autoregressive (FA‐Qual VAR) model to forecast industrial production growth, inflation, the Federal funds rate, and the term spread based on a pseudo out‐of‐sample recursive forecasting exercise over an out‐of‐sample period of 1980:1 to 2014:12, using an in‐sample period of 1960:1 to 1979:12. Short‐, medium‐, and long‐run horizons of 1, 6, 12, and 24 months ahead are considered. The forecast from the FA‐Qual VAR is compared with that of a standard VAR model, a Qual VAR model, and a factor‐augmented VAR (FAVAR). In general, we observe that the FA‐Qual VAR tends to perform significantly better than the VAR, Qual VAR and FAVAR (barring some exceptions relative to the latter). In addition, we find that the Qual VARs are also well equipped in forecasting probability of recessions when compared to probit models. 相似文献
46.
The predominantly marine genus Schizopera Sars, 1905 has only two significant inland water species-flocks, one in the ancient African Lake Tanganyika and the other in subterranean waters of Western Australia. Discovery of Schizopera abei sp. nov. from several interstitial locations in the vicinity of the ancient Lake Biwa has wider implications for the study of morphological homoplasies in the genus, as well as for the study of freshwater invasions in harpacticoid copepods. The new Schizopera species belongs to a small group of congeners with a two-segmented endopod of the fourth leg, which used to be recognised as a separate genus, Schizoperopsis Apostolov, 1982. Our reconstructed phylogenies based on the mtCOI partial sequences suggest that this character probably evolved convergently in at least some Schizopera, thus rendering the genus Schizoperopsis polyphyletic. However, almost all basal nodes in our cladograms are weakly supported, which shows limitations of a single-gene approach for reconstructing phylogenetic relationships. The new species is the first member of its genus from Japanese inland waters, and it has no close relatives among extent congeners anywhere in the world. We speculate that its ancestor may have invaded Lake Biwa, and subsequently its surrounding subterranean waters, from brackish areas around central Japan, presumably during a period of high sea water level through its major outflow river. This discovery may provide further support for the hypothesis about the role of ancient lakes as biodiversity pumps for subterranean habitats.http://zoobank.org/urn:lsid:zoobank.org:pub:1F71F7AD-B7C8-4AD3-BE44-5E1BEE4E2AA8 相似文献
47.
Morelli G Song Y Mazzoni CJ Eppinger M Roumagnac P Wagner DM Feldkamp M Kusecek B Vogler AJ Li Y Cui Y Thomson NR Jombart T Leblois R Lichtner P Rahalison L Petersen JM Balloux F Keim P Wirth T Ravel J Yang R Carniel E Achtman M 《Nature genetics》2010,42(12):1140-1143
Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs. 相似文献
48.
This paper examines the justification for the hypothesis of extended cognition (HEC). HEC claims that human cognitive processes can, and often do, extend outside our head to include objects in the environment. HEC has been justified by inference to the best explanation (IBE). Both advocates and critics of HEC claim that we can infer the truth value of HEC based on whether HEC makes a positive or negative explanatory contribution to cognitive science. I argue that IBE cannot play this epistemic role. A serious rival to HEC exists with a differing truth value, and this invalidates IBEs for both the truth and the falsity of HEC. Explanatory value to cognitive science is not a guide to the truth value of HEC. 相似文献
49.
Nikolina Vlatković Mark T. Boyd Carlos P. Rubbi 《Cellular and molecular life sciences : CMLS》2014,71(5):771-791
Nucleoli perform a crucial cell function, ribosome biogenesis, and of critical relevance to the subject of this review, they are also extremely sensitive to cellular stresses, which can cause loss of function and/or associated structural disruption. In recent years, we have learned that cells take advantage of this stress sensitivity of nucleoli, using them as stress sensors. One major protein regulated by this role of nucleoli is the tumor suppressor p53, which is activated in response to diverse cellular injuries in order to exert its onco-protective effects. Here we discuss a model of nucleolar regulation of p53, which proposes that key steps in the promotion of p53 degradation by the ubiquitin ligase MDM2 occur in nucleoli, thus providing an explanation for the observed link between nucleolar disruption and p53 stability. We review current evidence for this compartmentalization in p53 homeostasis and highlight current limitations of the model. Interestingly, a number of current chemotherapeutic agents capable of inducing a p53 response are likely to do so by targeting nucleolar functions and these compounds may serve to inform further improved therapeutic targeting of nucleoli. 相似文献
50.
Dawn M. Walker Steve Oghumu Gaurav Gupta Bradford S. McGwire Mark E. Drew Abhay R. Satoskar 《Cellular and molecular life sciences : CMLS》2014,71(7):1245-1263
Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality. 相似文献