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Hepatocellular carcinoma is generally refractory to clinical treatment. Here, we report that inactivation of the MYC oncogene is sufficient to induce sustained regression of invasive liver cancers. MYC inactivation resulted en masse in tumour cells differentiating into hepatocytes and biliary cells forming bile duct structures, and this was associated with rapid loss of expression of the tumour marker alpha-fetoprotein, the increase in expression of liver cell markers cytokeratin 8 and carcinoembryonic antigen, and in some cells the liver stem cell marker cytokeratin 19. Using in vivo bioluminescence imaging we found that many of these tumour cells remained dormant as long as MYC remain inactivated; however, MYC reactivation immediately restored their neoplastic features. Using array comparative genomic hybridization we confirmed that these dormant liver cells and the restored tumour retained the identical molecular signature and hence were clonally derived from the tumour cells. Our results show how oncogene inactivation may reverse tumorigenesis in the most clinically difficult cancers. Oncogene inactivation uncovers the pluripotent capacity of tumours to differentiate into normal cellular lineages and tissue structures, while retaining their latent potential to become cancerous, and hence existing in a state of tumour dormancy.  相似文献   
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Gene duplication and alternative splicing are distinct evolutionary mechanisms that provide the raw material for new biological functions. We explored their relationships in human and mouse and found an inverse correlation between the size of a gene's family and its use of alternatively spliced isoforms. A cross-organism analysis suggests that selection for genome-wide genic proliferation might be interchangeably met by either evolutionary mechanism.  相似文献   
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热轧带钢层流冷却设定模型的开发与实现   总被引:2,自引:1,他引:2  
分析了热轧带钢层流冷却的传热过程,基于传热过程给出了冷却控制的空冷和水冷温降计算模型,该模型为线性回归模型,不同于理论的指数温降模型,回归数据取自于现场,更具有实用性,具有模型结构简单、精度高的特点·对层流冷却的设定计算(预设定和修正设定计算)的程序实现方法进行了详细描述,讨论了层流冷却系统中的组别划分,并给出了冷却控制系统的数据流程·本系统的冷却能力强,具有较宽的冷却速率调整范围,运行情况以及使用控制效果良好,能满足现场生产以及新品种开发的要求·  相似文献   
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Obesity as a medical problem   总被引:128,自引:0,他引:128  
Kopelman PG 《Nature》2000,404(6778):635-643
Obesity is now so common within the world's population that it is beginning to replace undernutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart disease, certain forms of cancer, and sleep-breathing disorders. Obesity is defined by a body-mass index (weight divided by square of the height) of 30 kg m(-2) or greater, but this does not take into account the morbidity and mortality associated with more modest degrees of overweight, nor the detrimental effect of intra-abdominal fat. The global epidemic of obesity results from a combination of genetic susceptibility, increased availability of high-energy foods and decreased requirement for physical activity in modern society. Obesity should no longer be regarded simply as a cosmetic problem affecting certain individuals, but an epidemic that threatens global well being.  相似文献   
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