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排序方式: 共有164条查询结果,搜索用时 234 毫秒
151.
Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres 总被引:62,自引:0,他引:62
Lin J Wu H Tarr PT Zhang CY Wu Z Boss O Michael LF Puigserver P Isotani E Olson EN Lowell BB Bassel-Duby R Spiegelman BM 《Nature》2002,418(6899):797-801
152.
Martin J Han C Gordon LA Terry A Prabhakar S She X Xie G Hellsten U Chan YM Altherr M Couronne O Aerts A Bajorek E Black S Blumer H Branscomb E Brown NC Bruno WJ Buckingham JM Callen DF Campbell CS Campbell ML Campbell EW Caoile C Challacombe JF Chasteen LA Chertkov O Chi HC Christensen M Clark LM Cohn JD Denys M Detter JC Dickson M Dimitrijevic-Bussod M Escobar J Fawcett JJ Flowers D Fotopulos D Glavina T Gomez M Gonzales E Goodstein D Goodwin LA Grady DL Grigoriev I Groza M Hammon N Hawkins T 《Nature》2004,432(7020):988-994
153.
Grimwood J Gordon LA Olsen A Terry A Schmutz J Lamerdin J Hellsten U Goodstein D Couronne O Tran-Gyamfi M Aerts A Altherr M Ashworth L Bajorek E Black S Branscomb E Caenepeel S Carrano A Caoile C Chan YM Christensen M Cleland CA Copeland A Dalin E Dehal P Denys M Detter JC Escobar J Flowers D Fotopulos D Garcia C Georgescu AM Glavina T Gomez M Gonzales E Groza M Hammon N Hawkins T Haydu L Ho I Huang W Israni S Jett J Kadner K Kimball H Kobayashi A Larionov V Leem SH Lopez F Lou Y Lowry S 《Nature》2004,428(6982):529-535
Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu. 相似文献
154.
Voinnet O 《Nature genetics》2004,36(12):1245-1246
155.
The anterior pituitary of teleosts is unique among vertebrates in receiving a direct innervation which represents the morphological support of the neuroendocrine control of pars distalis functions. The participation of GABAergic fibers in this innervation was studied by means of immunocytochemistry at the light and electron microscopic levels, using antibodies against GABA. Immunoreactive fibers, characterized by the presence of small clear and dense cored vesicles, were detected in all parts of the gland. Immunopositive terminals were found in close, sometimes synaptic-like, contact with most glandular cell types in the anterior lobe. The data strongly suggest that in teleosts, as in mammals, GABA is involved in the neuroendocrine control of anterior pituitary functions. 相似文献
156.
Darrigol O 《Studies in history and philosophy of science》2003,34(3):515-573
In 1887 Helmholtz discussed the foundations of measurement in science as a last contribution to his philosophy of knowledge. This essay borrowed from earlier debates on the foundations of mathematics (Grassmann / Du Bois), on the possibility of quantitative psychology (Fechner / Kries, Wundt / Zeller), and on the meaning of temperature measurement (Maxwell, Mach). Late nineteenth-century scrutinisers of the foundations of mathematics (Dedekind, Cantor, Frege, Russell) made little of Helmholtz’s essay. Yet it inspired two mathematicians with an eye on physics (Poincaré and Hölder), and a few philosopher-physicists (Mach, Duhem, Campbell). The aim of the present paper is to situate Helmholtz’s contribution in this complex array of nineteenth-century philosophies of number, quantity, and measurement. 相似文献
157.
158.
Laguette N Sobhian B Casartelli N Ringeard M Chable-Bessia C Ségéral E Yatim A Emiliani S Schwartz O Benkirane M 《Nature》2011,474(7353):654-657
The primate lentivirus auxiliary protein Vpx counteracts an unknown restriction factor that renders human dendritic and myeloid cells largely refractory to HIV-1 infection. Here we identify SAMHD1 as this restriction factor. SAMHD1 is a protein involved in Aicardi-Goutières syndrome, a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response. We show that Vpx induces proteasomal degradation of SAMHD1. Silencing of SAMHD1 in non-permissive cell lines alleviates HIV-1 restriction and is associated with a significant accumulation of viral DNA in infected cells. Concurrently, overexpression of SAMHD1 in sensitive cells inhibits HIV-1 infection. The putative phosphohydrolase activity of SAMHD1 is probably required for HIV-1 restriction. Vpx-mediated relief of restriction is abolished in SAMHD1-negative cells. Finally, silencing of SAMHD1 markedly increases the susceptibility of monocytic-derived dendritic cells to infection. Our results demonstrate that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle. 相似文献
159.
Janoueix-Lerosey I Lequin D Brugières L Ribeiro A de Pontual L Combaret V Raynal V Puisieux A Schleiermacher G Pierron G Valteau-Couanet D Frebourg T Michon J Lyonnet S Amiel J Delattre O 《Nature》2008,455(7215):967-970
Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments. 相似文献
160.
A constitutive law for dense granular flows 总被引:7,自引:0,他引:7