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排序方式: 共有82条查询结果,搜索用时 15 毫秒
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Haigis KM Kendall KR Wang Y Cheung A Haigis MC Glickman JN Niwa-Kawakita M Sweet-Cordero A Sebolt-Leopold J Shannon KM Settleman J Giovannini M Jacks T 《Nature genetics》2008,40(5):600-608
Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways. 相似文献
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人工引入核电站排放的关键核素 ̄(131)I,采用γ能谱和总β计数两种方法确定核素在土壤-蔬菜系统中的转移系数。测得核素不同迁移时间、不同生长期的蔬菜、以及土壤中不同核素浓度等各种情况下的转移系数。给出转移系数的频数分布及变异性。γ能谱法测得的 ̄(131)I在广东土壤-蔬菜系统中转移系数的观察值范围为1.28×10 ̄(-2)~2.10×10 ̄(-1),几何平均值为5.05×10 ̄(-2),几何标准偏差为1.96.实验中观察到蔬菜棵株大小、不同气候条件等因素对转移系数的影响。 相似文献
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Thibault ST Singer MA Miyazaki WY Milash B Dompe NA Singh CM Buchholz R Demsky M Fawcett R Francis-Lang HL Ryner L Cheung LM Chong A Erickson C Fisher WW Greer K Hartouni SR Howie E Jakkula L Joo D Killpack K Laufer A Mazzotta J Smith RD Stevens LM Stuber C Tan LR Ventura R Woo A Zakrajsek I Zhao L Chen F Swimmer C Kopczynski C Duyk G Winberg ML Margolis J 《Nature genetics》2004,36(3):283-287
With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences. 相似文献
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采用雪崩热电子注入技术和高频C-V准静态C-V特性测试,研究了新型快速热氮化的SiOxNy介质膜界面陷阱的特征,侧重于研究界面陷阱的特性与分布。结果表明:这种SiOxNy薄膜禁带中央界面陷阱密度随氮化时间的分布变化呈现”回转效应“,且存在着不同类型、密度悬殊很大的电子陷阱、指出雪崩热电子注入过程中在Si/SiOxNy界面上产生两种性质不同的快界面态陷阱;给出了这两种界面态陷阱密度在禁带中能量的分布 相似文献
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Mitogens trigger a calcium-independent signal for proliferation in phorbol-ester-treated lymphocytes
The activation of T lymphocytes by mitogens requires at least two signals; the first, delivered to T cells by a mitogen in conjunction with accessory cells (monocytes/macrophages), leads to the generation of the second signal, interleukin-2 (IL-2). The first signal also induces the expression of IL-2 receptors on the surface of a subpopulation of T cells; binding of IL-2 to its receptor then initiates a cascade of events culminating in DNA synthesis by these cells. Certain compounds act synergistically with mitogens in promoting T-cell proliferation by substituting for the activities of interacting cells or their products. For example, the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) has been shown to restore the ability of macrophage-depleted T-cell populations to respond to mitogenic lectins. Transmembrane fluxes of calcium, leading to increased free cytosolic calcium concentrations ([Ca2+]), have been demonstrated following mitogen binding to lymphocytes and have been implicated in the initiation of cell proliferation. We show here that the effect of TPA on lymphocyte proliferation occurs in the absence of extracellular Ca2+ or detectable changes in [Ca2+]i, but only in the presence of mitogens. This suggests that in cells which have been incubated with the phorbol ester, mitogens can induce proliferation by a calcium-independent signal. 相似文献
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This paper presents a new spatial dependence model with an adjustment of feature difference. The model accounts for the spatial autocorrelation in both the outcome variables and residuals. The feature difference adjustment in the model helps to emphasize feature changes across neighboring units, while suppressing unobserved covariates that are present in the same neighborhood. The prediction at a given unit incorporates components that depend on the differences between the values of its main features and those of its neighboring units. In contrast to conventional spatial regression models, our model does not require a comprehensive list of global covariates necessary to estimate the outcome variable at the unit, as common macro-level covariates are differenced away in the regression analysis. Using the real estate market data in Hong Kong, we applied Gibbs sampling to determine the posterior distribution of each model parameter. The result of our empirical analysis confirms that the adjustment of feature difference with an inclusion of the spatial error autocorrelation produces better out-of-sample prediction performance than other conventional spatial dependence models. In addition, our empirical analysis can identify components with more significant contributions. 相似文献
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Grace W. C. Cheung Andrea Kokorovic Tony K. T. Lam 《Cellular and molecular life sciences : CMLS》2009,66(18):3023-3027
Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt
appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced
gut–brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal
lipid-induced gut–brain–liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will
focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids. 相似文献
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