全文获取类型
收费全文 | 1136篇 |
免费 | 6篇 |
国内免费 | 8篇 |
专业分类
系统科学 | 16篇 |
丛书文集 | 1篇 |
教育与普及 | 6篇 |
理论与方法论 | 16篇 |
现状及发展 | 119篇 |
研究方法 | 201篇 |
综合类 | 666篇 |
自然研究 | 125篇 |
出版年
2021年 | 6篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 15篇 |
2013年 | 15篇 |
2012年 | 94篇 |
2011年 | 236篇 |
2010年 | 39篇 |
2009年 | 5篇 |
2008年 | 92篇 |
2007年 | 98篇 |
2006年 | 96篇 |
2005年 | 85篇 |
2004年 | 92篇 |
2003年 | 75篇 |
2002年 | 78篇 |
2001年 | 6篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1978年 | 5篇 |
1976年 | 3篇 |
1973年 | 1篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 5篇 |
1969年 | 5篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1958年 | 1篇 |
1948年 | 1篇 |
1946年 | 2篇 |
排序方式: 共有1150条查询结果,搜索用时 15 毫秒
321.
Identification of ten loci associated with height highlights new biological pathways in human growth 总被引:1,自引:0,他引:1
Lettre G Jackson AU Gieger C Schumacher FR Berndt SI Sanna S Eyheramendy S Voight BF Butler JL Guiducci C Illig T Hackett R Heid IM Jacobs KB Lyssenko V Uda M;Diabetes Genetics Initiative;FUSION;KORA;Prostate Lung Colorectal Ovarian Cancer Screening Trial;Nurses' Health Study;SardiNIA Boehnke M Chanock SJ Groop LC Hu FB Isomaa B Kraft P Peltonen L Salomaa V Schlessinger D Hunter DJ Hayes RB Abecasis GR Wichmann HE Mohlke KL Hirschhorn JN 《Nature genetics》2008,40(5):584-591
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. 相似文献
322.
323.
Cotton RG; Human Variome Project Appelbe W Auerbach AD Becker K Bodmer W Boone DJ Boulyjenkov V Brahmachari S Brody L Brookes A Brown AF Byers P Cantu JM Cassiman JJ Claustres M Concannon P Cotton RG den Dunnen JT Flicek P Gibbs R Hall J Hasler J Katz M Kwok PY Laradi S Lindblom A Maglott D Marsh S Masimirembwa CM Minoshima S de Ramirez AM Pagon R Ramesar R Ravine D Richards S Rimoin D Ring HZ Scriver CR Sherry S Shimizu N Stein L Tadmouri GO Taylor G Watson M 《Nature genetics》2007,39(4):433-436
Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization-cosponsored meeting on June 20-23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations. 相似文献
324.
Guo DC Pannu H Tran-Fadulu V Papke CL Yu RK Avidan N Bourgeois S Estrera AL Safi HJ Sparks E Amor D Ades L McConnell V Willoughby CE Abuelo D Willing M Lewis RA Kim DH Scherer S Tung PP Ahn C Buja LM Raman CS Shete SS Milewicz DM 《Nature genetics》2007,39(12):1488-1493
The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin (encoded by ACTA2) and the beta-myosin heavy chain (encoded by MYH11). Here we show that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrate that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta. 相似文献
325.
326.
Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death 总被引:1,自引:0,他引:1
Baines CP Kaiser RA Purcell NH Blair NS Osinska H Hambleton MA Brunskill EW Sayen MR Gottlieb RA Dorn GW Robbins J Molkentin JD 《Nature》2005,434(7033):658-662
Mitochondria play a critical role in mediating both apoptotic and necrotic cell death. The mitochondrial permeability transition (mPT) leads to mitochondrial swelling, outer membrane rupture and the release of apoptotic mediators. The mPT pore is thought to consist of the adenine nucleotide translocator, a voltage-dependent anion channel, and cyclophilin D (the Ppif gene product), a prolyl isomerase located within the mitochondrial matrix. Here we generated mice lacking Ppif and mice overexpressing cyclophilin D in the heart. Ppif null mice are protected from ischaemia/reperfusion-induced cell death in vivo, whereas cyclophilin D-overexpressing mice show mitochondrial swelling and spontaneous cell death. Mitochondria isolated from the livers, hearts and brains of Ppif null mice are resistant to mitochondrial swelling and permeability transition in vitro. Moreover, primary hepatocytes and fibroblasts isolated from Ppif null mice are largely protected from Ca2+-overload and oxidative stress-induced cell death. However, Bcl-2 family member-induced cell death does not depend on cyclophilin D, and Ppif null fibroblasts are not protected from staurosporine or tumour-necrosis factor-alpha-induced death. Thus, cyclophilin D and the mitochondrial permeability transition are required for mediating Ca2+- and oxidative damage-induced cell death, but not Bcl-2 family member-regulated death. 相似文献
327.
328.
Chendrimada TP Gregory RI Kumaraswamy E Norman J Cooch N Nishikura K Shiekhattar R 《Nature》2005,436(7051):740-744
329.
330.
Microbial expansion following faunal mass extinctions in Earth history can be studied by petrographic examination of microbialites (microbial crusts) or well-preserved organic-walled microbes. However, where preservation is poor, quantification of microbial communities can be problematic. We have circumvented this problem by adopting a lipid biomarker-based approach to evaluate microbial community changes across the Permo/Triassic (P/Tr) boundary at Meishan in South China. We present here a biomarker stratigraphic record showing episodic microbial changes coupled with a high-resolution record of invertebrate mass extinction. Variation in the microbial community structure is characterized by the 2-methylhopane (2-MHP) index (a ratio of the abundance of cyanobacterial biomarkers to more general bacterial biomarkers). Two episodes of faunal mass extinction were each preceded by minima in the 2-MHP index, followed by strong maxima, likely reflecting microbial responses to the catastrophic events that caused the extinction and initiated ecosystem changes. Hence, both cyanobacterial biomarker and invertebrate fossil records provide evidence for two episodes of biotic crisis across the P/Tr boundary. 相似文献