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排序方式: 共有4809条查询结果,搜索用时 78 毫秒
151.
Kharchenko PV Alekseyenko AA Schwartz YB Minoda A Riddle NC Ernst J Sabo PJ Larschan E Gorchakov AA Gu T Linder-Basso D Plachetka A Shanower G Tolstorukov MY Luquette LJ Xi R Jung YL Park RW Bishop EP Canfield TK Sandstrom R Thurman RE MacAlpine DM Stamatoyannopoulos JA Kellis M Elgin SC Kuroda MI Pirrotta V Karpen GH Park PJ 《Nature》2011,471(7339):480-485
Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function. 相似文献
152.
Determining the signalling pathways that direct tissue expansion is a principal goal of regenerative biology. Vigorous pancreatic β-cell replication in juvenile mice and humans declines with age, and elucidating the basis for this decay may reveal strategies for inducing β-cell expansion, a long-sought goal for diabetes therapy. Here we show that platelet-derived growth factor receptor (Pdgfr) signalling controls age-dependent β-cell proliferation in mouse and human pancreatic islets. With age, declining β-cell Pdgfr levels were accompanied by reductions in β-cell enhancer of zeste homologue 2 (Ezh2) levels and β-cell replication. Conditional inactivation of the Pdgfra gene in β-cells accelerated these changes, preventing mouse neonatal β-cell expansion and adult β-cell regeneration. Targeted human PDGFR-α activation in mouse β-cells stimulated Erk1/2 phosphorylation, leading to Ezh2-dependent expansion of adult β-cells. Adult human islets lack PDGF signalling competence, but exposure of juvenile human islets to PDGF-AA stimulated β-cell proliferation. The discovery of a conserved pathway controlling age-dependent β-cell proliferation indicates new strategies for β-cell expansion. 相似文献
153.
Bonfoh B Raso G Koné I Dao D Girardin O Cissé G Zinsstag J Utzinger J Tanner M 《Nature》2011,474(7353):569-571
154.
橡胶支座水平剪切弹塑性力学性能试验研究 总被引:1,自引:0,他引:1
通过对铅芯橡胶支座剪切弹塑性力学性能试验,发现铅芯橡胶支座的滞回曲线与加载时程密切相关,在同一水平应变下,水平剪切刚度随加载次数的增多有所减小,最后趋于稳定;在不同应变下,水平剪切刚度随应变的增大而减小.试验还表明铅芯橡胶支座不仅在大应变存在着小应变滞回特性,而且在小应变也存在着小应变滞回特性. 相似文献
155.
Experimental study of heat transfer of ultra-supercritical pressure water in vertical upward internally ribbed tube 总被引:2,自引:0,他引:2
王为术 《高技术通讯(英文版)》2007,13(1):17-22
Under ultra-supercritical pressure, the heat transfer characteristics of water in vertical upward 4-head internally ribbed tubes with a diameter of 28.65mm and thickness of 8mm were experimentally studied. The experiments were performed at P=25~34MPa, G=450~1800kg/(m2·s) and q=200~600kW/m2. The results show that the pressure has only a moderate effect on the heat transfer of ultra-supercritical water when the water temperature is below the pseudocritical point. Sharp rise of the wall temperature near the pesudocritical region occurs earlier at a higher pressure. Increasing the mass velocity improves the heat transfer with a much stronger effect below the pesudocritical point than that above the pesudocritical point. For given pressure and mass velocity, the inner wall heat flux also shows a significant effect on the inner wall temperature, with a higher inner wall heat flux leading to a higher inner wall temperature. Increasing of inner wall heat flux leads to an early occurrence of sharp rise of the wall temperature. Correlations of heat transfer coefficients are also presented for vertical upward internally ribbed tubes. 相似文献
156.
157.
158.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
159.
针对大型复杂产品,传统基于模型的系统工程(model-based system engineering, MBSE)方法存在系统设计和仿真验证的多语言、多平台集成实现,难以保证高效、准确地反馈系统设计的缺陷,无法达到快速优化设计目的等问题,提出采用基于面向复杂系统支持MBSE的新一代一体化建模仿真语言—X语言实现面向起飞场景的民机跨域子系统的一体化建模仿真。从民机起飞过程需求分析出发,建立了起飞场景的系统级模型和物理级模型,并在X语言的建模仿真软件—XLab进行统一的建模仿真验证,给出了基于X语言面向复杂产品协同设计与仿真一体化方法,为不同领域的设计人员实现复杂产品设计的协同与优化提供了全新的理论与方法参考。 相似文献
160.
针对空间主动碎片清除操作中连续型三臂节机器人系统跟踪问题,提出一种基于强化学习的自适应滑模控制算法。基于数据驱动的建模方法,采用BP神经网络对三臂节连续型机械臂进行建模,并作为预测模型指导强化学习实时调节所提出滑模控制器的控制参数,从而实现连续型机器人运动的实时跟踪控制。仿真结果表明:提出的数据驱动的预测模型对随机轨迹预测的相对误差保持在±1%以内,能够高精度地反映系统动态特性。对比固定参数的滑模控制器,提出的自适应控制器在保证系统达到控制目标的同时具有更低的超调量和更短的调节时间,表现出更好的控制效果。 相似文献