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341.
Rajagopalan H Bardelli A Lengauer C Kinzler KW Vogelstein B Velculescu VE 《Nature》2002,418(6901):934
Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer. 相似文献
342.
RhoA/Rho激酶在大鼠阴茎勃起机制中的调节作用 总被引:11,自引:1,他引:10
一般认为一氧化氮(nitric oxide,NO)释放增加促进小动脉和海绵体平滑肌舒张是导致男性阴茎勃起的主要机制。研究发现内源性血管收缩因子对维持阴茎萎状态有重要作用。应用大鼠模型活体检测使用Y-27632拮抗Rho-激酶活性后对阴茎勃起生理机制的影响;应用免疫转印技术检测 阴茎海绵体内RhoA和Rho激酶蛋白的表达。结果显示在大鼠海绵体组织内有内源性RhoA和Rho激酶蛋白的表达和存在;Y-27632海绵体内注射阻滞RhoA/Rho激酶活性使ICP和CCP/MAP比值明显升高;局部小剂量应用Y-27632对MAP没有明显影响;Y-27632可增强系列电刺激引起的由NO介导的CCP/MAP比值的增加;NO合成酶和鸟苷酸环化酶抑制剂的作用不能阻滞RhoA/Rho激酶抑制剂对大鼠阴茎海绵体平滑肌的松弛作用和CCP/MAP的增加。说明RhoA/Rho激酶信号系统发挥了维持海绵体萎软状态重要作用,这是与NO介导途径不同的阴茎勃起生理调节机制。RhoA/Rho激酶抑制剂可能是ED治疗的新领域新方法。 相似文献
343.
344.
Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. 总被引:11,自引:0,他引:11
Michael G Anderson Richard S Smith Norman L Hawes Adriana Zabaleta Bo Chang Janey L Wiggs Simon W M John 《Nature genetics》2002,30(1):81-85
Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma. DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (GpnmbR150X) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to GpnmbR150X; otherwise, similar D2 mice that are not homozygous for GpnmbR150X do not develop IPD. ISA is caused by the recessive Tyrp1b mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma. 相似文献
345.
以对苯半醌负离子自由基为模型 ,利用ESR技术研究黄酮类化合物清除自由基的作用 ,初步获得一些构效关系。 相似文献
346.
目的是将用于测量片状试样的热扩散率的激光闪光法推广至测量薄膜试样。应用 1 5纳秒脉冲 Nd:YAG激光及响应时间 0 .9微秒的 (Hg,Cd) Te红外探测器等建立了闪光法热扩散率测量系统 ,并应用此系统对微米量级厚度的不锈钢薄膜进行了测量。同时针对将激光闪光法应用于薄膜时所出现的问题 ,如激光的有限脉冲时间及有限吸收厚度效应 ,测量系统的滞后效应 ,以及增强红外吸收及辐射用表面黑化膜的影响进行了分析并提出了解决方法 相似文献
347.
B.Wünnemann 《科学通报(英文版)》2002,47(23):1946-1956
Comprehensive field investigations and laboratory analyses show that palaeolakes, including fresh- mesohaline water Megalake Tengger and other semi-con- nected, isolated water bodies, during late Pleistocene covered an area of more than 20000 km2, which is more than half of the Tengger Desert in NW China. Stratigraphic correlation and chronological evidence indicate that before ca. 42000 aBP the area was more arid. The palaeolakes started to develop around 40000 uncal. 14C aBP but until 37000 14C aBP their scope was limited. High water levels established from 35000 14C aBP lasted until 22000 14CaBP. Lake levels regressed between 22000 and 20000 14C aBP but transgressed from 20000 to 18600 14C aBP. Subsequently, water level declined further and the Megalake Tengger finally desiccated at around 18000 14C aBP. Megalake Tengger possessed a fresh-mesohaline water property, implying that the regional precipitation increased significantly. During the period of Megalake Tengger, the climate was warmer-humid than present. The annual rainfall was 250 to 350 mm more than that of today and the temperature was 1.5 to 3.0℃ higher. 相似文献
348.
Zircon (U-Th)/He thermochronological constraints on Cretaceous thermal extension of Dabieshan orogen 总被引:1,自引:0,他引:1
:(U-Th)/He ages of 13 samples from Yuexi-Luotian core and its flanks in Dabieshan orogen fall in the range of 155~85 Ma. He ages for samples from the core range between 85~107 Ma, while those from the flanks range between 114~155 Ma. The result shows that the Yuexi-Luotian core was a thermal dome in Cretaceous with core temperature being much higher than those of the flanks. The thermal extension which resulted in the formation of Dabie core complex lasted until ca. 85 Ma. The magnitude of exhumation in the core is approximately 1528.8 m more than that in the flanks. 相似文献
349.
提出了一种由样品辨识、模糊推理和控制处理 3个子网模块构成的基于知识的多层神经网络 .这种网络由各子网分别构成并按照最初的模糊控制结构适当连接而建立 ,具有明确区分各组成子网功能及其知识流结构 .由于综合了模糊逻辑的推理过程及神经网络的学习能力 ,使它能够在其结构中以模糊规则的形式引入语言知识并通过网络的训练及自学习对这些知识进行加工 ,从而实现了真正意义上的自适应模糊控制器 .最后还讨论了这种 NFN网络在动态过程控制中的应用 相似文献
350.