全文获取类型
收费全文 | 230篇 |
免费 | 14篇 |
国内免费 | 98篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 7篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 2篇 |
2014年 | 1篇 |
2013年 | 4篇 |
2012年 | 13篇 |
2011年 | 16篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 8篇 |
2007年 | 9篇 |
2006年 | 10篇 |
2005年 | 47篇 |
2004年 | 50篇 |
2003年 | 4篇 |
2002年 | 12篇 |
2001年 | 20篇 |
2000年 | 61篇 |
1999年 | 21篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有342条查询结果,搜索用时 15 毫秒
21.
22.
CC to TT mutation in the mitochondrial DNA of normal skin: relationship to ultraviolet light exposure 总被引:1,自引:0,他引:1
We have previously reported that ultraviolet (UV)-specific (CC to TT) mutations in p53 gene can be detected in normal skin. This, however, cannot be used as a cumulative marker of UV exposure, since cells with the p53 mutation acquire a clonal growth advantage. Moreover, a large skin biopsy is necessary for each assay. In order to circumvent these problems, we have measured mitochondrial (Mt) DNA mutations; there are more than 1000 copies of the Mt genome per cell, and Mt genes are not directly involved in cell growth. We have established a sensitive allele-specific polymerase chain reaction (AS-PCR) assay capable of detecting one CC to TT mutation in Mt DNA among 10(7) wild-type genes using a mismatch allele-specific primer. With this assay, we found no mutation-positive samples from internal non-exposed tissue (stomach, colon, and blood) (0/50). In contrast, 17 out of 111 skin samples were positive: the mutation frequency in positive samples was around 10(7)-10(-6) (10-100 copies of mutant in 10(8) wild-type Mt DNA). In normal skin tissue, the prevalence of positive samples was higher in those from exposed sites (13/51) than in those from less-exposed sites (1/26) (p<0.05). However, a quantitative correlation between sunlight exposure and the accumulation of mutations was not found. We conclude that the UV exposure-associated CC to TT mutation in Mt DNA can be detected in normal skin, but that further studies are required to develop this as a quantitative marker for UV exposure. 相似文献
23.
25.
木质素过氧化物酶是一种重要的具有工业应用前景的木质素降解酶,但已报道真菌来源的木质素过氧化物酶只能在酸性低温条件下发挥作用,限制了其进一步的工业应用.通过培养一株耐热耐碱放线茵——绿色糖单孢茵发酵产酶,采用DEAE-Cellulose,CM-Cellulose和Superdex 75凝胶过滤层析等分离纯化方法,得到一种具有耐热耐碱特性的木质素过氧化物酶.经凝胶电泳检测其为单一蛋白,分子量为41 kD.最终纯化倍数达到20倍,活性回收率为6%.采用LTQ法对纯酶进行蛋白质归类鉴定,得到其部分氨基酸片段,为该酶的进一步分子生物学研究奠定基础. 相似文献
26.
International Parkinson's Disease Genomics Consortium 《PLoS genetics》2011,7(6):e1002142
A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson''s Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson''s disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5×10−10, PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci. 相似文献
27.
CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies 总被引:26,自引:0,他引:26 下载免费PDF全文
CHEK Breast Cancer Case-Control Consortium 《American journal of human genetics》2004,74(6):1175-1182
Previous studies of families with multiple cases of breast cancer have indicated that a frameshift alteration in the CHEK2 gene, 1100delC, is associated with an elevated frequency of breast cancer in such families, but the risk associated with the variant in other situations is uncertain. To evaluate the breast cancer risk associated with this variant, 10,860 breast cancer cases and 9,065 controls from 10 case-control studies in five countries were genotyped. CHEK2*1100delC was found in 201 cases (1.9%) and 64 controls (0.7%) (estimated odds ratio 2.34; 95% CI 1.72–3.20; P=.0000001). There was some evidence of a higher prevalence of CHEK2*1100delC among cases with a first-degree relative affected with breast cancer (odds ratio 1.44; 95% CI 0.93–2.23; P=.10) and of a trend for a higher breast cancer odds ratio at younger ages at diagnosis (P=.002). These results confirm that CHEK2*1100delC confers an increased risk of breast cancer and that this risk is apparent in women unselected for family history. The results are consistent with the hypothesis that CHEK2*1100delC multiplies the risks associated with susceptibility alleles in other genes to increase the risk of breast cancer. 相似文献
28.
Zhe REN Chuan-hai ZHANG Lian-jun WANG Yun-xia CUI Ren-bin QI Chong-ren YANG Ying-jun ZHANG Xiao-yi WEI Da-xiang LU** Yi-fei WANG ** 《Virologica Sinica》2010,(2)
Herpes simplex virus type 1 (HSV-1) is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum (level) Hutch (Celastraceae) is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared ... 相似文献
29.
C Xie Xc ZS Zhou X Xae Xee N Li Xe Y Bian X YJ Wang Xb Xc Xefa LJ Wang Xb Xed Xaf BL Li Xe Xff Xf BL Song Xbb Xfdd Xeae 《Journal of lipid research》2012,53(10):2092-2101
The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo. 相似文献
30.
I Feinkohl N Sattar P Welsh RM Reynolds IJ Deary MW Strachan JF Price;on behalf of the Edinburgh Type Diabetes Study 《PloS one》2012,7(9):e44569