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排序方式: 共有465条查询结果,搜索用时 15 毫秒
401.
Turner DJ Miretti M Rajan D Fiegler H Carter NP Blayney ML Beck S Hurles ME 《Nature genetics》2008,40(1):90-95
Meiotic recombination between highly similar duplicated sequences (nonallelic homologous recombination, NAHR) generates deletions, duplications, inversions and translocations, and it is responsible for genetic diseases known as 'genomic disorders', most of which are caused by altered copy number of dosage-sensitive genes. NAHR hot spots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at four NAHR hot spots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that (i) these NAHR hot spots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been underascertained clinically, most notably that resulting from the duplication of 7q11, the reciprocal of the deletion causing Williams-Beuren syndrome. 相似文献
402.
提出了一种直观,高效地用于概念设计作用图的等手输入,进行几何变形的方法,采用此方法可以徒手输入两笔曲线(参考曲线和目标曲线),并据此二曲线来移动多边形模型的顶点,从而达到变形三维模型的目的,解决了大曲率变形时产生的自相关问题,另外,还可用来定义变形影响区域。 相似文献
403.
采用网格再划分技术的网格推延造型 总被引:1,自引:1,他引:0
提出了一种对自由多边形物体直观高效的三维网格推延造型方法,采用这种造型方法,用户可以在已有的三维物体上勾勒两笔二维轮廓,从而推延了新的空间网格曲面,阐述了两种网格再划分技术,网格优化和网格细分,在此基础上,详细介绍了网格推延造型的方法,该方法能广泛地应用于多边形物体的自由造型。 相似文献
404.
Electrostatic orientation during electron transfer between flavodoxin and cytochrome c 总被引:5,自引:0,他引:5
Various studies have shown that reaction rates between reversibly binding electron transfer proteins depend strongly on solution ionic strength. These observations suggest that intermolecular electrostatic interactions are important in facilitating the formation of a productive reaction complex. A recently examined system involves the reduction of vertebrate cytochrome c by bacterial flavodoxin. Although this is a nonphysiological reaction, it proceeds with rates typical for natural partners and is similarly inhibited at high ionic strengths. Here we describe computational studies which examine the role of electrostatics in the formation of a putative reaction complex between flavodoxin and cytochrome c. The results suggest that electrostatic interactions preorient the molecules before they make physical contact, facilitating the formation of an optimal reaction complex. 相似文献
405.
Matthew J. Brown 《Studies in history and philosophy of science》2009,40(2):213-220
Ron Giere’s recent book Scientific perspectivism sets out an account of science that attempts to forge a via media between two popular extremes: absolutist, objectivist realism on the one hand, and social constructivism or skeptical anti-realism on the other. The key for Giere is to treat both scientific observation and scientific theories as perspectives, which are limited, partial, contingent, context-, agent- and purpose-dependent, and pluralism-friendly, while nonetheless world-oriented and modestly realist. Giere’s perspectivism bears significant similarity to earlier ideas of Paul Feyerabend and John Dewey. Comparing these to Giere’s work not only uncovers a consilience of ideas, but also can help to fill out Giere’s account in places where it is not fully developed, as well as helping us understand the work of these earlier authors and their continuing relevance to contemporary concerns in philosophy of science. 相似文献
406.
407.
Stephens P Edkins S Davies H Greenman C Cox C Hunter C Bignell G Teague J Smith R Stevens C O'Meara S Parker A Tarpey P Avis T Barthorpe A Brackenbury L Buck G Butler A Clements J Cole J Dicks E Edwards K Forbes S Gorton M Gray K Halliday K Harrison R Hills K Hinton J Jones D Kosmidou V Laman R Lugg R Menzies A Perry J Petty R Raine K Shepherd R Small A Solomon H Stephens Y Tofts C Varian J Webb A West S Widaa S Yates A Brasseur F Cooper CS Flanagan AM Green A Knowles M Leung SY Looijenga LH 《Nature genetics》2005,37(6):590-592
We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure. 相似文献
408.
Hahn MW Mezey JG Begun DJ Gillespie JH Kern AD Langley CH Moyle LC 《Nature》2005,433(7023):E5-6; discussion E7-8
The idea that natural selection on genes might be detected using only a single genome has been put forward by Plotkin and colleagues, who present a method that they claim can detect selection without the need for comparative data and which, if correct, would confer greater power of analysis with less information. Here we argue that their method depends on assumptions that confound their conclusions and that, even if these assumptions were valid, the authors' inferences about adaptive natural selection are unjustified. 相似文献
409.
Real-time forecasts of tomorrow's earthquakes in California 总被引:4,自引:0,他引:4
Despite a lack of reliable deterministic earthquake precursors, seismologists have significant predictive information about earthquake activity from an increasingly accurate understanding of the clustering properties of earthquakes. In the past 15 years, time-dependent earthquake probabilities based on a generic short-term clustering model have been made publicly available in near-real time during major earthquake sequences. These forecasts describe the probability and number of events that are, on average, likely to occur following a mainshock of a given magnitude, but are not tailored to the particular sequence at hand and contain no information about the likely locations of the aftershocks. Our model builds upon the basic principles of this generic forecast model in two ways: it recasts the forecast in terms of the probability of strong ground shaking, and it combines an existing time-independent earthquake occurrence model based on fault data and historical earthquakes with increasingly complex models describing the local time-dependent earthquake clustering. The result is a time-dependent map showing the probability of strong shaking anywhere in California within the next 24 hours. The seismic hazard modelling approach we describe provides a better understanding of time-dependent earthquake hazard, and increases its usefulness for the public, emergency planners and the media. 相似文献
410.
Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H 总被引:22,自引:0,他引:22
Pickering MC Cook HT Warren J Bygrave AE Moss J Walport MJ Botto M 《Nature genetics》2002,31(4):424-428
The alternative pathway of complement is activated continuously in vivo through the C3 'tick-over' pathway. This pathway is triggered by the hydrolysis of C3, resulting in the formation of C3 convertase. This, in turn, generates C3b, which mediates many of the biological functions of complement. Factor H, the main regulator of this activation, prevents formation and promotes dissociation of the C3 convertase enzyme, and, together with factor I, mediates the proteolytic inactivation of C3b. Factor H deficiency, described in 29 individuals from 12 families and in pigs, allows unhindered activation of fluid-phase C3 and severe depletion of plasma C3 (ref. 11). Membranoproliferative glomerulonephritis (MPGN) occurs in factor H-deficient humans and pigs. Although MPGN has been reported in other conditions in which uncontrolled activation of C3 occurs, the role of C3 dysregulation in the pathogenesis of MPGN is not understood. Here we show that mice deficient in factor H (Cfh(-/-) mice) develop MPGN spontaneously and are hypersensitive to developing renal injury caused by immune complexes. Introducing a second mutation in the gene encoding complement factor B, which prevents C3 turnover in vivo, obviates the phenotype of Cfh(-/-) mice. Thus, uncontrolled C3 activation in vivo is essential for the development of MPGN associated with deficiency of factor H. 相似文献