全文获取类型
收费全文 | 211篇 |
免费 | 43篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 7篇 |
2020年 | 9篇 |
2019年 | 13篇 |
2018年 | 12篇 |
2017年 | 9篇 |
2016年 | 12篇 |
2015年 | 21篇 |
2014年 | 16篇 |
2013年 | 19篇 |
2012年 | 15篇 |
2011年 | 19篇 |
2010年 | 14篇 |
2009年 | 11篇 |
2008年 | 10篇 |
2007年 | 9篇 |
2006年 | 3篇 |
2005年 | 8篇 |
2004年 | 3篇 |
2003年 | 5篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1967年 | 1篇 |
1951年 | 2篇 |
排序方式: 共有255条查询结果,搜索用时 15 毫秒
1.
2.
Y H Hsiang G D Berkovitz T R Brown C J Migeon A M Brodie 《Journal of steroid biochemistry》1987,26(1):131-135
4-hydroxy-4-androstene-3,17-dione (4-OHA) has been shown to be a potent inhibitor of aromatase activity. It is effective in the control of estrogen-dependent processes in female subjects and may potentially be useful in the treatment of estrogen-dependent processes in men. Human foreskin fibroblasts grown in cell culture provide a model to investigate the effects of 4-OHA on extraglandular aromatase activity as well as the ability of the compound to influence androgen receptor binding and the 5 alpha-reduction of testosterone (T). Initial experiments were carried out to determine the potency of 4-OHA in genital skin fibroblasts by incubating cells with 4-OHA over a range of concentrations. When aromatase activity was determined at a substrate concentration close to the apparent Km of the enzyme, a 44% inhibition of enzyme activity occurred at a mean concentration of 5 nM 4-OHA. Enzyme kinetic studies analyzed by Eadie-Hofstee plots demonstrated competitive inhibition by 4-OHA with a mean apparent Ki of 2.7 nM. When 5 alpha-reductase activity was determined in the presence of 200 nM [3H]T, in the absence or presence of 4-OHA, a 50% inhibition of enzyme activity occurred at an inhibitor concentration of 3 microM. In androgen receptor binding studies, 4-OHA possessed 1% of the affinity of dihydrotestosterone (DHT) for [3H]DHT binding sites. In summary: 4-OHA is a potent and specific inhibitor of aromatase activity in human genital skin fibroblasts, the affinity of the enzyme for 4-OHA being greater than its affinity for the substrate, androstenedione. The influence of 4-OHA on 5 alpha-reductase activity and androgen receptor binding is minimal. 相似文献
3.
Y H Hsiang R Hertzberg S Hecht L F Liu 《The Journal of biological chemistry》1985,260(27):14873-14878
Camptothecin, a cytotoxic drug, is a strong inhibitor of nucleic acid synthesis in mammalian cells and a potent inducer of strand breaks in chromosomal DNA. Neither the equilibrium dialysis nor the unwinding measurement indicates any interaction between camptothecin and purified DNA. However, camptothecin induces extensive single strand DNA breaks in reactions containing purified mammalian DNA topoisomerase I. DNA breakage in vitro is immediate and reversible. Analyses of camptothecin-induced DNA breaks show that topoisomerase I is covalently linked to the 3' end of the broken DNA. In addition, camptothecin inhibits the catalytic activity of mammalian DNA topoisomerase I. We propose that camptothecin blocks the rejoining step of the breakage-reunion reaction of mammalian DNA topoisomerase I. This blockage results in the accumulation of a cleavable complex which resembles the transient intermediate proposed for eukaryotic DNA topoisomerase I. The inhibition of nucleic acid synthesis and the induction of DNA strand breaks observed in vivo may be related to the formation of this drug-induced cleavable complex. 相似文献
4.
被囊动物中生物活性物质研究的一些进展 总被引:1,自引:0,他引:1
本文对近年从海鞘中提取分离的环肽类及生物碱类化合物作了综述,对一些典型化合物如Didemnins、Patellamides、Merdine、Eudistomins及Ecteinascidins等作了较详细的介绍。 相似文献
5.
本文报道流行性出血热病毒(汉坦病毒)H-114株的电镜形态。发现形态发生以内质网膜和胞浆膜芽生为主。病毒颗粒为圆形或卵圆形。具有双层膜结构,大小为90~120nm。提出了汉坦病毒形态发生的理论观点。 相似文献
6.
Epidemic hemorrhagic fever in Hubei Province, The People's Republic of China: a clinical and serological study 总被引:1,自引:0,他引:1
M S Cohen J Casals G D Hsiung H E Kwei C C Chin H C Ge C M Hsiang P W Lee C J Gibbs D C Gajdusek 《The Yale journal of biology and medicine》1981,54(1):41-55
Between July 1975 and April 1980, 71 patients were admitted to the Second Attached Hospital of Hubei Provincial Medical College in Wuchang with the diagnosis of epidemic hemorrhagic fever (EHF). The clinical course among these patients was similar to that described for patients with Korean hemorrhagic fever, and hemorrhagic fever with renal syndrome of the U.S.S.R. The overall mortality was 11.2 percent. Sera obtained from some of these patients as well as from patients admitted to the First Attached Hospital of Hubei Provincial Medical College were tested against an antigen associated with Korean hemorrhagic fever and showed exceedingly high antibody titers. We conclude that EHF in Central China represents the same or a closely related disease process as Korean hemorrhagic fever. 相似文献
7.
Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c‐MYC axis in breast cancer
Yan Liu Hang Song Shiyi Yu Kuo‐Hsiang Huang Xinxing Ma Yehui Zhou Shuang Yu Jingzhong Zhang Liming Chen 《Journal of cellular and molecular medicine》2020,24(3):2135-2144
Breast cancer is the second leading death cause of cancer death for all women. Previous study suggested that Protein Kinase D3 (PRKD3) was involved in breast cancer progression. In addition, the protein level of PRKD3 in triple‐negative breast adenocarcinoma was higher than that in normal breast tissue. However, the oncogenic mechanisms of PRKD3 in breast cancer is not fully investigated. Multi‐omic data showed that ERK1/c‐MYC axis was identified as a major pivot in PRKD3‐mediated downstream pathways. Our study provided the evidence to support that the PRKD3/ERK1/c‐MYC pathway play an important role in breast cancer progression. We found that knocking out PRKD3 by performing CRISPR/Cas9 genome engineering technology suppressed phosphorylation of both ERK1 and c‐MYC but did not down‐regulate ERK1/2 expression or phosphorylation of ERK2. The inhibition of ERK1 and c‐MYC phosphorylation further led to the lower protein level of c‐MYC and then reduced the expression of the c‐MYC target genes in breast cancer cells. We also found that loss of PRKD3 reduced the rate of the cell proliferation in vitro and tumour growth in vivo, whereas ectopic (over)expression of PRKD3, ERK1 or c‐MYC in the PRKD3‐knockout breast cells reverse the suppression of the cell proliferation and tumour growth. Collectively, our data strongly suggested that PRKD3 likely promote the cell proliferation in the breast cancer cells by activating ERK1‐c‐MYC axis. 相似文献
8.
9.
ChiWei Yeh WeiChieh Huang PangHung Hsu KunHai Yeh LiChin Wang Paul WeiChe Hsu HsiuChuan Lin YiNing Chen ShuChuan Chen ChenHsiang Yeang HsuehChi S Yen 《The EMBO journal》2021,40(7)
Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino‐ or carboxyl‐termini are eliminated by the N‐ or C‐degron pathways, respectively. We aimed to elucidate the function of C‐degron pathways and to unveil how normal proteomes are exempt from C‐degron pathway‐mediated destruction. Our data reveal that C‐degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C‐degron and N‐degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C‐degron pathways, but not of defective proteins, suggesting proteolysis‐based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways. 相似文献
10.