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排序方式: 共有972条查询结果,搜索用时 546 毫秒
891.
892.
Global analysis of protein phosphorylation in yeast 总被引:1,自引:0,他引:1
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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
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RNA interference in adult mice 总被引:203,自引:0,他引:203
RNA interference is an evolutionarily conserved surveillance mechanism that responds to double-stranded RNA by sequence-specific silencing of homologous genes. Here we show that transgene expression can be suppressed in adult mice by synthetic small interfering RNAs and by small-hairpin RNAs transcribed in vivo from DNA templates. We also show the therapeutic potential of this technique by demonstrating effective targeting of a sequence from hepatitis C virus by RNA interference in vivo. 相似文献
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899.
For over a century, numerous undocumented reports have appeared about unusual large-scale luminous phenomena above thunderclouds and, more than 80 years ago, it was suggested that an electrical discharge could bridge the gap between a thundercloud and the upper atmosphere. Since then, two classes of vertically extensive optical flashes above thunderclouds have been identified-sprites and blue jets. Sprites initiate near the base of the ionosphere, develop very rapidly downwards at speeds which can exceed 107 m s-1 (ref. 15), and assume many different geometrical forms. In contrast, blue jets develop upwards from cloud tops at speeds of the order of 105 m s-1 and are characterized by a blue conical shape. But no experimental data related to sprites or blue jets have been reported which conclusively indicate that they establish a direct path of electrical contact between a thundercloud and the lower ionosphere. Here we report a video recording of a blue jet propagating upwards from a thundercloud to an altitude of about 70 km, taken at the Arecibo Observatory, Puerto Rico. Above an altitude of 42 km-normally the upper limit for blue jets and the lower terminal altitude for sprites-the flash exhibited some features normally observed in sprites. As we observed this phenomenon above a relatively small thunderstorm cell, we speculate that it may be common and therefore represent an unaccounted for component of the global electric circuit. 相似文献
900.
Large seasonal and hemispheric asymmetries in the martian climate system are generally ascribed to variations in solar heating associated with orbital eccentricity. As the orbital elements slowly change (over a period of >104 years), characteristics of the climate such as dustiness and the vigour of atmospheric circulation are thought to vary, as should asymmetries in the climate (for example, the deposition of water ice at the northern versus the southern pole). Such orbitally driven climate change might be responsible for the observed layering in Mars' polar deposits by modulating deposition of dust and water ice. Most current theories assume that climate asymmetries completely reverse as the angular distance between equinox and perihelion changes by 180 degrees. Here we describe a major climate mechanism that will not precess in this way. We show that Mars' global north-south elevation difference forces a dominant southern summer Hadley circulation that is independent of perihelion timing. The Hadley circulation, a tropical overturning cell responsible for trade winds, largely controls interhemispheric transport of water and the bulk dustiness of the atmosphere. The topography therefore imprints a strong handedness on climate, with water ice and the active formation of polar layered deposits more likely in the north. 相似文献