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国家自然科学基金(30024001)

作品数:6 被引量:16H指数:2
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发文基金:国家自然科学基金国家重点基础研究发展计划国家高技术研究发展计划更多>>
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核仁和核仁蛋白被引量:2
2004年
核仁是位于细胞核内的非膜结构。电子显微镜下的核仁从形态上可以分为三层结构包括纤维中心区(FC)、高密度纤维区(DFC)和颗粒区(GC)。核仁内的蛋白有核糖体蛋白和非核糖体蛋白两种。利用蛋白质组学方法已经鉴定了350多种核仁蛋白,其中包括80多种核糖体蛋白。核仁是核糖体合成的场所,核仁中的非核糖体蛋白对核糖体的生物合成起关键调控作用。核仁不仅是细胞内通讯和核糖体RNA加工的中心,而且在细胞周期、细胞增殖和衰老中起重要调控作用;核仁也是tRNA、mRNA和其它类型小分子RNA加工的场所。因此核仁是一个多功能的细胞生命活动中心。
周光金余龙赵寿元
关键词:核仁核仁蛋白细胞核电子显微镜RNA
中国肝癌病人p53突变体R248W的细胞功能研究被引量:1
2008年
【目的】探索p53基因突变对细胞正常功能的影响,阐明肝癌的发病机制。【方法】利用PCR产物直接测序的方法,对202例中国肝癌患者p53基因的11个外显子进行突变筛查;利用定点突变的方法构建真核表达载体pCMV-R248W,Western blot检测突变体蛋白R248W在p53缺失型H1299细胞中的表达情况;采用双荧光素酶报告基因检测系统和流式细胞仪,研究R248W突变对转录活性及促凋亡能力的影响。【结果】在其中1例样本的7号外显子处筛查到突变形式为CGG→TGG的点突变,使p53蛋白248位的精氨酸(Arg)突变为色氨酸(Trp),即R248W,突变率为0.495%;在H1299细胞中转染等量的pCMV-p53和pCMV-R248W时,野生型p53与突变体R248W的蛋白表达量相当,但R248W的转录活性及促凋亡能力显著低于野生型p53。【结论】R248W突变可能引起p53蛋白构象的改变,从而影响p53的转录活性及促凋亡能力,使细胞的正常生理功能紊乱,导致肿瘤发生。
赵晶郭泽坤
关键词:P53突变WESTERNBLOT转录活性凋亡
人类基因组上的假基因被引量:9
2004年
假基因是基因组上与编码基因序列非常相似的非功能性基因组DNA拷贝,一般情况都不被转录,且没有明确生理意义。假基因根据其来源可分为复制假基因和已加工假基因。迄今为止,明确鉴定的人类假基因多为已加工假基因,有8000个之多。在Swiss-Prot/TrEMBL收录的编码蛋白质的将近25500个基因序列中,约10%在基因组中有一个或多个近全长已加工假基因。其余的功能基因都没有已加工假基因。核糖体蛋白基因具有最多数量的已加工假基因,约有l700个(占已加工假基因数的22%),少数基因,如cyclophilinA、肌动蛋白(actin)、角蛋白(keratin)、GAPDH、细胞色素C(cytochromec)和nucleophosmin等则有很多份已加工假基因。总体上讲,假基因在人类染色体上的分布与染色体长度成比例,但已加工假基因在GC含量为41%~46%的染色体区域密度最高。已加工假基因的拷贝数和功能基因在生殖器官中的表达高度一致,说明许多假基因发生在胚胎阶段,另外也和基因中GC含量和基因大小密切相关。假基因的准确鉴定对基因组进化、分子医学研究和医学应用具有重要意义。
周光金余龙赵寿元
关键词:基因组分子进化
中国肝细胞癌p53基因热点突变R249S的载体构建及其在细胞中的表达
2007年
抑癌基因p53突变是人肝细胞癌(Hepatocellular carcinoma,HCC)中常见的现象,中国江苏启东地区的HCC患者中p53基因的第249位密码子突变AGG→AGT/Arg→Ser(R249S)被认为是热点突变。本研究以人肝cDNA为模板,扩增人全长p53基因,将其克隆到pCMV-Myc载体中。利用定点突变引物以pC-MV-p53为模板,构建R249S定点突变体pCMV-R249S,转染p53缺陷型的H1299细胞系。Western Blot检测表明,克隆在pCMV-Myc载体中的p53基因和249位密码子热点突变的p53基因都可以在H1299细胞系中表达。
赵晶郭泽坤
关键词:HCC热点突变CDNA定点突变WESTERNBLOT
TP53 Arg72Pro polymorphism is associated with esophageal cancer risk:A meta-analysis被引量:4
2011年
AIM:To investigate the association between TP53 Arg72Pro polymorphism and esophageal cancer(EC)risk using meta-analysis. METHODS:All eligible studies published before March 1,2010 were selected by searching PubMed using keywords"p53"or"TP53","polymorphism"or"variation", "esophageal"and"cancer"or"carcinoma".Crude odds ratios(ORs)with 95%confidence intervals(CIs)were assessed for EC risk associated with TP53 Arg72Pro polymorphism using fixed-and random-effects models. RESULTS:Nine case-control studies involving 5545 subjects were included in this meta-analysis.Significantly reduced risk of EC was associated with TP53genotypes for Arg/Arg+Arg/Pro vs Pro/Pro(OR= 0.73,95%CI:0.57-0.94,P=0.014).Subgroup analyses according to the source of controls and the specimens used for determining TP53 Arg72Pro genotypes or sample size showed that significantly reduced risk was observed only in studies which have populationbased controls(Arg/Arg vs Pro/Pro:OR=0.56,95% CI:0.47-0.66,P<0.001),and use white blood cells or normal tissue to assess TP53 genotypes of cases (Arg/Arg vs Pro/Pro:OR=0.56,95%CI:0.47-0.65,P <0.001)or include at least 200 subjects(Arg/Arg vs Pro/Pro:OR=0.56,95%CI:0.47-0.65,P<0.001). Analysis restricted to well-designed studies also supported the significantly decreased risk of EC(Arg/Arg vs Pro/Pro:OR=0.54,95%CI:0.46-0.64,P<0.001). CONCLUSION:TP53 Arg72 carriers are significantly associated with decreased EC risk.Nevertheless,more welldesigned studies are needed to confirm our findings.
De-Ke Jiang Lei Yao Wen-Zhang Wang Bo Peng Wei-Hua Ren Xian-Mei Yang Long Yu
关键词:P53基因随机效应模型
Literature and patent analysis of the cloning and identification of human functional genes in China
2012年
The Human Genome Project was launched at the end of the 1980s.Since then,the cloning and identification of functional genes has been a major focus of research across the world.In China too,the potentially profound impact of such studies on the life sciences and on human health was realized,and relevant studies were initiated in the 1990s.To advance China's involvement in the Human Genome Project,in the mid-1990s,Committee of Experts in Biology from National High Technology Research and Development Program of China(863 Program) proposed the "two 1%" goal.This goal envisaged China contributing 1% of the total sequencing work,and cloning and identifying 1% of the total human functional genes.Over the past 20 years,tremendous achievement has been accomplished by Chinese scientists.It is well known that scientists in China finished the 1% of sequencing work of the Human Genome Project,whereas,there is no comprehensive report about "whether China had finished cloning and identifying 1% of human functional genes".In the present study,the GenBank database at the National Center of Biotechnology Information,the PubMed search tool,and the patent database of the State Intellectual Property Office,China,were used to retrieve entries based on two screening standards:(i) Were the newly cloned and identified genes first reported by Chinese scientists?(ii) Were the Chinese scientists awarded the gene sequence patent? Entries were retrieved from the databases up to the cut-off date of 30 June 2011 and the obtained data were analyzed further.The results showed that 589 new human functional genes were first reported by Chinese scientists and 159 gene sequences were patented(http:gene.fudan.sh.cn/introduction/database/chinagene/chinagene.html).This study systematically summarizes China's contributions to human functional genomics research and answers the question "has China finished cloning and identifying 1% of human functional genes?" in the affirmative.
XIA YanTANG LiShaYAO LeiWAN BoYANG XianMeiYU Long
关键词:人类基因组计划功能基因组学中国科学家GENBANK数据库
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