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91.
基于一篇文章所引用的参考文献和该文的被引频次两个维度,提出了衡量该文外显成长度的相对指标.该研究涉及的引用数据及每条参考文献的被引数据均来自网络版科学引文索引(Web of Science),检索日期为2010年4月最后一周. 相似文献
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Sahin E Colla S Liesa M Moslehi J Müller FL Guo M Cooper M Kotton D Fabian AJ Walkey C Maser RS Tonon G Foerster F Xiong R Wang YA Shukla SA Jaskelioff M Martin ES Heffernan TP Protopopov A Ivanova E Mahoney JE Kost-Alimova M Perry SR Bronson R Liao R Mulligan R Shirihai OS Chin L DePinho RA 《Nature》2011,470(7334):359-365
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Inuzuka H Shaik S Onoyama I Gao D Tseng A Maser RS Zhai B Wan L Gutierrez A Lau AW Xiao Y Christie AL Aster J Settleman J Gygi SP Kung AL Look T Nakayama KI DePinho RA Wei W 《Nature》2011,471(7336):104-109
The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer and T-cell acute lymphoblastic leukaemia (T-ALL). In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL, validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun, Myc, cyclin E and notch 1 (ref. 9), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth, overexpression of Jun, Myc or notch 1 can also induce programmed cell death. Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Myc and/or notch 1. Here we show that the E3 ubiquitin ligase SCF(FBW7) (a SKP1-cullin-1-F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7-deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL. 相似文献
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Summary Sequential chromatographic fractionation ofRhodnius prolixus midgut homogenate yielded only one endopeptidase, but revealed the presence of carboxypeptidase-A and B-like enzymes, di- and tripeptidases, as well as aminopeptidase activities.Work subsidized by FINEP and CNPq, Rio and FAPESP, São paulo. 相似文献
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F Pichinoty J L Garcia M Mandel C Job M Durand 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1978,286(19):1403-1405
Ten bacteria of the genus Bacillus were isolated from pasteurized soils, in anaerobiosis and at 32 degrees C, on peptone broth containing 0.5% KNO2. They are Gram variable rods producing oval spores. They are oxidase positive and have catalase. They grow, in anaerobiosis, on NO-3, NO-2, N2O, and NO as respiratory electron acceptors. These compounds are reduced to N2. 相似文献
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Slow inward calcium currents have no obvious role in muscle excitation-contraction coupling 总被引:11,自引:0,他引:11
It has been proposed that an influx of calcium ions into twitch muscle fibres during an action potential might initiate contraction. However, when external Ca2+ is lowered to 10(-8) M with EGTA, the fibres can produce normal twitches for many minutes. Nevertheless, a clear Ca2+ influx during contraction has been demonstrated, and it has been found that phasic skeletal muscle has an inward calcium current (ICa) which can give rise to calcium spikes. In certain conditions, a reduction in external Ca2+ with 80-90 mM EGTA results in reversible blockade of excitation-contraction (e-c) coupling, leading some authors to suggest that extracellular Ca2+ moved into the myoplasm due to ICa may be involved in the e-c coupling mechanism that triggers contraction. This proposition was further supported by the localization of ICa in the T-system, which circumvented the problem of the delay due to calcium diffusion from the surface membrane. We have now investigated whether ICa has a clear role in initiating or sustaining contractions in twitch muscle fibres. Our approach was to decrease or eliminate ICa with the calcium-blocking agent diltiazem (Herbesser) and to see how the twitch, tetanic and potassium-contracture tensions were affected. We found that ICa could be decreased or cancelled with the calcium-blocking agent, but that the same concentration of the drug potentiated the twitch, tetanus and contractures. We conclude, therefore, that ICa has no role in e-c coupling. A preliminary report of these results has been presented elsewhere. 相似文献