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A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo 总被引:77,自引:0,他引:77
M H Rosner M A Vigano K Ozato P M Timmons F Poirier P W Rigby L M Staudt 《Nature》1990,345(6277):686-692
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A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia 总被引:1,自引:0,他引:1
E Fainstein C Marcelle A Rosner E Canaani R P Gale O Dreazen S D Smith C M Croce 《Nature》1987,330(6146):386-388
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Shah SP Roth A Goya R Oloumi A Ha G Zhao Y Turashvili G Ding J Tse K Haffari G Bashashati A Prentice LM Khattra J Burleigh A Yap D Bernard V McPherson A Shumansky K Crisan A Giuliany R Heravi-Moussavi A Rosner J Lai D Birol I Varhol R Tam A Dhalla N Zeng T Ma K Chan SK Griffith M Moradian A Cheng SW Morin GB Watson P Gelmon K Chia S Chin SF Curtis C Rueda OM Pharoah PD Damaraju S Mackey J Hoon K Harkins T Tadigotla V Sigaroudinia M Gascard P Tlsty T Costello JF Meyer IM Eaves CJ Wasserman WW 《Nature》2012,486(7403):395-399
Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. 相似文献
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The incorporation of 3H-leucine into neurohypophyseal proteins was measured in vitro, 24 h after the administration of a single dose of estradiol (0.3 mug) to castrated female rats. Estradiol treatment caused a significant increase of 3H-leucine incorporation into proteins of the posterior lobe. The effects of estradiol depended largely upon time injection. Rats injected at 06.00 h, i.e., at the end of the dark period exhibited a 74% increase in protein synthesis, whereas rat injected at 14.00 h, i.e., at the middle of the light period only showed a 30% of increase. 相似文献
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低碳锰钢中周期性带状组织 总被引:6,自引:0,他引:6
用扫描电镜和电子探针研究了低碳锰钢中的周期性带状组织,结果表明,在全部研究用钢中,钢锭经热轧后均出现这种组织,其严重程度随钢的成分而异,并随坯带加工顺序而增加,带状组织与锰的显微偏析等因素有关,适当的调整碳锰以及形成模跨铁素体带的转变产物可降低带状组织的严重程度。 相似文献
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Insulin-degrading enzyme (IDE), a Zn2+-metalloprotease, is involved in the clearance of insulin and amyloid-beta (refs 1-3). Loss-of-function mutations of IDE in rodents cause glucose intolerance and cerebral accumulation of amyloid-beta, whereas enhanced IDE activity effectively reduces brain amyloid-beta (refs 4-7). Here we report structures of human IDE in complex with four substrates (insulin B chain, amyloid-beta peptide (1-40), amylin and glucagon). The amino- and carboxy-terminal domains of IDE (IDE-N and IDE-C, respectively) form an enclosed cage just large enough to encapsulate insulin. Extensive contacts between IDE-N and IDE-C keep the degradation chamber of IDE inaccessible to substrates. Repositioning of the IDE domains enables substrate access to the catalytic cavity. IDE uses size and charge distribution of the substrate-binding cavity selectively to entrap structurally diverse polypeptides. The enclosed substrate undergoes conformational changes to form beta-sheets with two discrete regions of IDE for its degradation. Consistent with this model, mutations disrupting the contacts between IDE-N and IDE-C increase IDE catalytic activity 40-fold. The molecular basis for substrate recognition and allosteric regulation of IDE could aid in designing IDE-based therapies to control cerebral amyloid-beta and blood sugar concentrations. 相似文献
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D. P. Cardinali C. A. Nagle J. M. Rosner 《Cellular and molecular life sciences : CMLS》1974,30(10):1222-1223
Résumé Des homogénats de glande pineale de rat mâle métabolisèrent de la testostérone-C14 in vitro en stradiol-C14 et en strone-C14. Les métabolites furent identifiés chiomatographiquement et dans le cas de l'stradiol par recristallisation à activité spécifique constante. La conversion de la testostérone en stradiol fut de 0.19–0.27% et en strone de 0.02–0.04%. Ces résultatsci indiquent que la pinéale ressemble à d'autres régions du cerveau soumises au contrôle de la sécrétion de gonadotropines.
These studies were supported by grants from the Comisión Nacional de Estudios Geo-Heliofísicos, Argentina and the World Health Organization. D.P.C. and C.A.N. are established investigators of the Comisión Nacional de Estudios Geo-Heliofísicos. J.M.R. is an established investigator of the Consejo Nacional de Investigaciones Cientificas y Técnicas, Argentina. 相似文献
These studies were supported by grants from the Comisión Nacional de Estudios Geo-Heliofísicos, Argentina and the World Health Organization. D.P.C. and C.A.N. are established investigators of the Comisión Nacional de Estudios Geo-Heliofísicos. J.M.R. is an established investigator of the Consejo Nacional de Investigaciones Cientificas y Técnicas, Argentina. 相似文献
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