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排序方式: 共有163条查询结果,搜索用时 15 毫秒
51.
Stingl J Eirew P Ricketson I Shackleton M Vaillant F Choi D Li HI Eaves CJ 《Nature》2006,439(7079):993-997
Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium. 相似文献
52.
53.
In addition to its role as a tumour suppressor and cell-cycle checkpoint control protein, p53 has been implicated as an important protein in embryonic development. Despite the viability of most p53 null mice, evidence has accumulated that p53 may regulate differentiation and the response of embryonic cells to diverse environmental stresses. Moreover, it appears that maintenance of a fine balance of p53 protein levels within embryonic cells is important for optimal development. Inappropriate overexpression or underexpression of p53 can lead to embryonic lethality or increased risk of malformations. The p53 protein may utilize multiple functional activities in its regulation of developmental processes. 相似文献
54.
Law level of RRO(Repeatable Run Out), NRRO(Non Repe at able Run Out), and lightweight construction are a major trend in the high-speed HDD(Hard Disk Drive) sytem to reduce track misregestration and to achieve high track density, which lead to succeed in the market. However, it is not easy to r educe RRO, NRRO, and the weight of the spinning disk spindle system efficiently because lightweight construction and or bearing stiffness changes often yields a decrease in the static and dynamic stiffness of the ... 相似文献
55.
p53 mutant mice that display early ageing-associated phenotypes. 总被引:56,自引:0,他引:56
Stuart D Tyner Sundaresan Venkatachalam Jene Choi Stephen Jones Nader Ghebranious Herbert Igelmann Xiongbin Lu Gabrielle Soron Benjamin Cooper Cory Brayton Sang Hee Park Timothy Thompson Gerard Karsenty Allan Bradley Lawrence A Donehower 《Nature》2002,415(6867):45-53
The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing. 相似文献
56.
定向生长碳纳米管的研究进展 总被引:1,自引:0,他引:1
由于碳纳米管具有独特的结构和性能,因而自从被发现以来一直受到人们的关注,近年来,已利用各种方法成合成出碳纳米管,特别是利用化学气相沉积(CVD)方法制备了高度准直的碳纳米管,实现了碳纳米管的定向生长,使得碳纳米管具有更加广泛的应用价值和研究价值。本文综述了近几年CVD定向生长碳纳米管的方法和生长机制,分析和讨论了不同制备方法对碳纳米管生长过程的影响,同时还着重分析了催化剂颗粒在碳纳米管的生长过程中对定向生长碳纳米管的作用。 相似文献
57.
The structure of a protein depends critically on the complex interactions among its amino acid residues. It has long been hypothesized that interacting residues might tend to coevolve, but it is not known whether such coevolution is a general phenomenon across the proteome. Here, we describe a novel methodology called phylogeny-aided structural analysis, which uncovers robust signals of interacting-residue coevolution in mammalian proteomes. Furthermore, this new method allows the magnitude of coevolution to be quantified. Finally, it facilitates a comprehensive evaluation of various factors that affect interacting-residue coevolution, such as the physicochemical properties of the interactions between residues, solvent accessibility of the residues and their secondary structure context. 相似文献
58.
Choi MH Lee IK Kim GW Kim BU Han YH Yu DY Park HS Kim KY Lee JS Choi C Bae YS Lee BI Rhee SG Kang SW 《Nature》2005,435(7040):347-353
Platelet-derived growth factor (PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H2O2 (refs 1, 2-3). Mammalian 2-Cys peroxiredoxin type II (Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H2O2 produced in response to growth factors such as PDGF and epidermal growth factor; however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H2O2, enhanced activation of PDGF receptor (PDGFR) and phospholipase Cgamma1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H2O2 in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease. 相似文献
59.
Hattori M Fujiyama A Taylor TD Watanabe H Yada T Park HS Toyoda A Ishii K Totoki Y Choi DK Groner Y Soeda E Ohki M Takagi T Sakaki Y Taudien S Blechschmidt K Polley A Menzel U Delabar J Kumpf K Lehmann R Patterson D Reichwald K Rump A Schillhabel M Schudy A Zimmermann W Rosenthal A Kudoh J Schibuya K Kawasaki K Asakawa S Shintani A Sasaki T Nagamine K Mitsuyama S Antonarakis SE Minoshima S Shimizu N Nordsiek G Hornischer K Brant P Scharfe M Schon O Desario A Reichelt J Kauer G Blocker H 《Nature》2000,405(6784):311-319
Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes. 相似文献
60.
Redox modulation of the NMDA receptor 总被引:9,自引:0,他引:9
Redox modulation has been recognized to be an important mechanism of regulation for the N-methyl-D-aspartate (NMDA) receptor. Sulfhydryl reducing agents enhance, whereas oxidizing agents decrease, NMDA-evoked currents. Multiple cysteine residues located in different NMDA receptor subunits have been identified as molecular determinants underlying redox modulation. The NMDA receptor is also regulated by nitric oxide (NO)-related species directly, not involving cyclic GMP, but the molecular mechanism of this action has heretofore not been entirely clear. The confusion arose at least partly due to the fact that various redox forms of NO (NO+, NO*, NO-, each having an additional electron compared with the previous) have distinct mechanisms of action. Recently, a critical cysteine residue (Cys 399) on the NR2A subunit has been shown to react under physiological conditions with NO by S-nitrosylation (transfer of the NO+ to cysteine thiol) or by reaction with NO- (nitroxyl anion) to underlie this form of modulation. 相似文献