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排序方式: 共有297条查询结果,搜索用时 15 毫秒
171.
MA Deardorff M Bando R Nakato E Watrin T Itoh M Minamino K Saitoh M Komata Y Katou D Clark KE Cole E De Baere C Decroos N Di Donato S Ernst LJ Francey Y Gyftodimou K Hirashima M Hullings Y Ishikawa C Jaulin M Kaur T Kiyono PM Lombardi L Magnaghi-Jaulin GR Mortier N Nozaki MB Petersen H Seimiya VM Siu Y Suzuki K Takagaki JJ Wilde PJ Willems C Prigent G Gillessen-Kaesbach DW Christianson FJ Kaiser LG Jackson T Hirota ID Krantz K Shirahige 《Nature》2012,489(7415):313-317
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Mackay TF Richards S Stone EA Barbadilla A Ayroles JF Zhu D Casillas S Han Y Magwire MM Cridland JM Richardson MF Anholt RR Barrón M Bess C Blankenburg KP Carbone MA Castellano D Chaboub L Duncan L Harris Z Javaid M Jayaseelan JC Jhangiani SN Jordan KW Lara F Lawrence F Lee SL Librado P Linheiro RS Lyman RF Mackey AJ Munidasa M Muzny DM Nazareth L Newsham I Perales L Pu LL Qu C Ràmia M Reid JG Rollmann SM Rozas J Saada N Turlapati L Worley KC Wu YQ Yamamoto A Zhu Y Bergman CM Thornton KR 《Nature》2012,482(7384):173-178
A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics. 相似文献
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The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer 总被引:18,自引:0,他引:18
Lipkin SM Rozek LS Rennert G Yang W Chen PC Hacia J Hunt N Shin B Fodor S Kokoris M Greenson JK Fearon E Lynch H Collins F Gruber SB 《Nature genetics》2004,36(7):694-699
Most susceptibility to colorectal cancer (CRC) is not accounted for by known risk factors. Because MLH1, MSH2 and MSH6 mutations underlie high-penetrance CRC susceptibility in hereditary nonpolyposis colon cancer (HNPCC), we hypothesized that attenuated alleles might also underlie susceptibility to sporadic CRC. We looked for gene variants associated with HNPCC in Israeli probands with familial CRC unstratified with respect to the microsatellite instability (MSI) phenotype. Association studies identified a new MLH1 variant (415G-->C, resulting in the amino acid substitution D132H) in approximately 1.3% of Israeli individuals with CRC self-described as Jewish, Christian and Muslim. MLH1 415C confers clinically significant susceptibility to CRC. In contrast to classic HNPCC, CRCs associated with MLH1 415C usually do not have the MSI defect, which is important for clinical mutation screening. Structural and functional analyses showed that the normal ATPase function of MLH1 is attenuated, but not eliminated, by the MLH1 415G-->C mutation. The new MLH1 variant confers a high risk of CRC and identifies a previously unrecognized mechanism in microsatellite-stable tumors. These studies suggest that variants of mismatch repair proteins with attenuated function may account for a higher proportion of susceptibility to sporadic microsatellite-stable CRC than previously assumed. 相似文献
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As lithospheric plates are subducted, rocks are metamorphosed under high-pressure and ultrahigh-pressure conditions to produce eclogites and eclogite facies metamorphic rocks. Because chemical equilibrium is rarely fully achieved, eclogites may preserve in their distinctive mineral assemblages and textures a record of the pressures, temperatures and deformation the rock was subjected to during subduction and subsequent exhumation. Radioactive parent-daughter isotopic variations within minerals reveal the timing of these events. Here we present in situ zircon U/Pb ion microprobe data that dates the timing of eclogite facies metamorphism in eastern Papua New Guinea at 4.3 +/- 0.4 Myr ago, making this the youngest documented eclogite exposed at the Earth's surface. Eclogite exhumation from depths of approximately 75 km was extremely rapid and occurred at plate tectonic rates (cm yr(-1)). The eclogite was exhumed within a portion of the obliquely convergent Australian-Pacific plate boundary zone, in an extending region located west of the Woodlark basin sea floor spreading centre. Such rapid exhumation (> 1 cm yr(-1)) of high-pressure and, we infer, ultrahigh-pressure rocks is facilitated by extension within transient plate boundary zones associated with rapid oblique plate convergence. 相似文献
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The ability to deposit and tailor reliable semiconducting films (with a particular recent emphasis on ultrathin systems) is indispensable for contemporary solid-state electronics. The search for thin-film semiconductors that provide simultaneously high carrier mobility and convenient solution-based deposition is also an important research direction, with the resulting expectations of new technologies (such as flexible or wearable computers, large-area high-resolution displays and electronic paper) and lower-cost device fabrication. Here we demonstrate a technique for spin coating ultrathin (approximately 50 A), crystalline and continuous metal chalcogenide films, based on the low-temperature decomposition of highly soluble hydrazinium precursors. We fabricate thin-film field-effect transistors (TFTs) based on semiconducting SnS(2-x)Se(x) films, which exhibit n-type transport, large current densities (>10(5) A cm(-2)) and mobilities greater than 10 cm2 V(-1) s(-1)--an order of magnitude higher than previously reported values for spin-coated semiconductors. The spin-coating technique is expected to be applicable to a range of metal chalcogenides, particularly those based on main group metals, as well as for the fabrication of a variety of thin-film-based devices (for example, solar cells, thermoelectrics and memory devices). 相似文献