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排序方式: 共有759条查询结果,搜索用时 0 毫秒
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Lopatto D Alvarez C Barnard D Chandrasekaran C Chung HM Du C Eckdahl T Goodman AL Hauser C Jones CJ Kopp OR Kuleck GA McNeil G Morris R Myka JL Nagengast A Overvoorde PJ Poet JL Reed K Regisford G Revie D Rosenwald A Saville K Shaw M Skuse GR Smith C Smith M Spratt M Stamm J Thompson JS Wilson BA Witkowski C Youngblom J Leung W Shaffer CD Buhler J Mardis E Elgin SC 《Science (New York, N.Y.)》2008,322(5902):684-685
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Mao JH Kim IJ Wu D Climent J Kang HC DelRosario R Balmain A 《Science (New York, N.Y.)》2008,321(5895):1499-1502
The enzyme mTOR (mammalian target of rapamycin) is a major target for therapeutic intervention to treat many human diseases, including cancer, but very little is known about the processes that control levels of mTOR protein. Here, we show that mTOR is targeted for ubiquitination and consequent degradation by binding to the tumor suppressor protein FBXW7. Human breast cancer cell lines and primary tumors showed a reciprocal relation between loss of FBXW7 and deletion or mutation of PTEN (phosphatase and tensin homolog), which also activates mTOR. Tumor cell lines harboring deletions or mutations in FBXW7 are particularly sensitive to rapamycin treatment, which suggests that loss of FBXW7 may be a biomarker for human cancers susceptible to treatment with inhibitors of the mTOR pathway. 相似文献
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Steed PM Tansey MG Zalevsky J Zhukovsky EA Desjarlais JR Szymkowski DE Abbott C Carmichael D Chan C Cherry L Cheung P Chirino AJ Chung HH Doberstein SK Eivazi A Filikov AV Gao SX Hubert RS Hwang M Hyun L Kashi S Kim A Kim E Kung J Martinez SP Muchhal US Nguyen DH O'Brien C O'Keefe D Singer K Vafa O Vielmetter J Yoder SC Dahiyat BI 《Science (New York, N.Y.)》2003,301(5641):1895-1898
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands. 相似文献
66.
试论呼市地区园林植物五小害虫的发展状况和防治策略 总被引:1,自引:0,他引:1
本文在实地调查和试验研究的基础上,系统地分析了呼市地区园林植物五小害虫的发展状况,在初步查清主要危害虫种及其生物学特性基础上,提出了加强植物检疫,利用,保护天敌,加强生物防治的研究,适时采用物理防治方法,合理科学地应用化学防治法的综合防治策略,对化学杀虫剂的选择,使用浓度,施药时间和次数提出了科学有效的试验依据。 相似文献
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Guidotti LG Rochford R Chung J Shapiro M Purcell R Chisari FV 《Science (New York, N.Y.)》1999,284(5415):825-829
Viral clearance during hepatitis B virus (HBV) infection has been thought to reflect the destruction of infected hepatocytes by CD8(+) T lymphocytes. However, in this study, HBV DNA was shown to largely disappear from the liver and the blood of acutely infected chimpanzees long before the peak of T cell infiltration and most of the liver disease. These results demonstrate that noncytopathic antiviral mechanisms contribute to viral clearance during acute viral hepatitis by purging HBV replicative intermediates from the cytoplasm and covalently closed circular viral DNA from the nucleus of infected cells. 相似文献
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Treusch S Hamamichi S Goodman JL Matlack KE Chung CY Baru V Shulman JM Parrado A Bevis BJ Valastyan JS Han H Lindhagen-Persson M Reiman EM Evans DA Bennett DA Olofsson A DeJager PL Tanzi RE Caldwell KA Caldwell GA Lindquist S 《Science (New York, N.Y.)》2011,334(6060):1241-1245
Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system. 相似文献
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Measurements of surface ozone (O3) and nitrogen oxides (NO x ) were conducted at Tae-ahn (TAP) and Chongwon (CHN) on the Korean Peninsula, during the Aerosol Characterization Experiment—Asian Pacific region (ACE-Asia) campaign, March–May 2001. The measurements provide ground-based data at a western remote site of south Korea and characterize the long-range transport of O3 over the Yellow Sea region during spring. The mean values of O3 and NO2 concentration at TAP were 42 ppb and 12 ppb, respectively. The average O3 diurnal variation of 17 ppb at TAP indicates that the loss of O3 was not pronounced during the night. The highest NO2 concentrations, with an average diurnal variation of 8 ppb, occurred in the afternoon at 13–15 LST. The day-to-day variation of daily O3 concentrations at TAP is strongly influenced by the movement of synoptic scale weather patterns. In general, the O3 concentration in a southwesterly airflow tended to increase when a moving anticyclone crossed the site, ahead of a cold front. By contrast, north-northwesterly airflows associated with the passage of a cold front bring fresh continental outflow and decrease O3 concentrations. Surface O3 data at TAP were classified utilizing backward trajectory analysis based on the residence time, as well as the path of the airflows, in the boundary layer (1500 m asl) over the Yellow Sea region. The results show that north-northwest continental airflows, that were transported around Lake Baikal and eastern Mongolia at an altitude of approximately 3 km at relatively high speed and came straight down at TAP, represent continental background O3 concentrations with a mean value of 29 ppb for this period. These airflows have a short period of residence of less than one day in the boundary layer over the Yellow Sea region. In contrast, the mean O3 value of 45 ppb was observed in regionally polluted airflows mainly passing through the east-southeast part of China and remaining for 3 days, on average, in the Yellow Sea region. These three days residence time of the regionally polluted airflows over the Yellow Sea region allowed sufficient time for photochemical O3 formation. 相似文献