全文获取类型
收费全文 | 159篇 |
免费 | 1篇 |
专业分类
系统科学 | 1篇 |
教育与普及 | 1篇 |
理论与方法论 | 1篇 |
现状及发展 | 66篇 |
研究方法 | 13篇 |
综合类 | 77篇 |
自然研究 | 1篇 |
出版年
2019年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2012年 | 7篇 |
2011年 | 12篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 7篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 5篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1972年 | 4篇 |
1971年 | 7篇 |
1970年 | 4篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1967年 | 4篇 |
1966年 | 5篇 |
1965年 | 2篇 |
1963年 | 1篇 |
1962年 | 5篇 |
1959年 | 1篇 |
1957年 | 1篇 |
1946年 | 2篇 |
1945年 | 1篇 |
排序方式: 共有160条查询结果,搜索用时 328 毫秒
81.
Deficiency of Mbd2 suppresses intestinal tumorigenesis 总被引:16,自引:0,他引:16
Gene silencing through de novo methylation of CpG island promoters contributes to cancer. We find that Mbd2, which recruits co-repressor complexes to methylated DNA, is essential for efficient tumorigenesis in the mouse intestine. As Mbd2-deficient mice are viable and fertile, their resistance to intestinal cancer may be of therapeutic relevance. 相似文献
82.
83.
Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein 总被引:40,自引:0,他引:40
V K Chaudhary T Mizukami T R Fuerst D J FitzGerald B Moss I Pastan E A Berger 《Nature》1988,335(6188):369-372
It is projected that in the absence of effective therapy, most individuals infected with human immunodeficiency virus (HIV) will develop acquired immune deficiency syndrome (AIDS) and ultimately succumb to a combination of opportunistic microbial infections, malignancies and direct pathogenic effects of the virus. Anti-viral agents, immunomodulators, and inhibitors of specific HIV functions are being tested as potential treatments to alleviate the high morbidity and mortality. An alternative therapeutic concept involves the development of cytotoxic agents that are targeted to kill HIV-infected cells. Here we describe the purification and characterization of a recombinant protein produced in Escherichia coli that contains the HIV-binding portion of the human CD4 molecule linked to active regions of Pseudomonas exotoxin A. This hybrid protein displays selective toxicity toward cells expressing the HIV envelope glycoprotein and thus represents a promising novel therapeutic agent for the treatment of AIDS. 相似文献
84.
G. R. Pettit L. E. Houghton N. H. Rogers R. M. Coomes D. F. Berger P. R. Reucroft J. F. Day J. L. Hartwell H. B. Wood Jr. 《Cellular and molecular life sciences : CMLS》1972,28(4):381-382
Zusammenfassung Eine Voruntersuchung der Insektengruppe Lepidoptera auf anti-tumor-aktive Stoffe führte zu einer detaillierten chemischen Prüfung der aus Asien stammenden SchmetterlingeCatopsilia crocale Cramer (Pieridae) undPieris rapae cruavora. Ein bedeutender Teil der Anti-Tumor-Aktivität scheint ihren Ursprung in der chemischen Substanz Isoxanthopterin zu besitzen.
The present contribution represents Part XXVII of the series Antineoplastic Agents. For Part XXVI refer toG. R. Pettit, J. F. Day, J. L. Hartwell andH. B. Wood, Nature, Lond.227, 962 (1970).
This investigation was supported by Public Health Service Research Grants No. CA-10612-01 to No. CA-10612-04 from the National Cancer Institute, and was presented in part at the American Chemical Society Meeting, Washington, D.C., September 1971. We are also grateful to the National Science Foundation for financial assistance (Grant numbers GB-4939 and GB-6979) used in obtaining the Atlas CH-4B and SM-1B mass spectrometers employed in this study. 相似文献
The present contribution represents Part XXVII of the series Antineoplastic Agents. For Part XXVI refer toG. R. Pettit, J. F. Day, J. L. Hartwell andH. B. Wood, Nature, Lond.227, 962 (1970).
This investigation was supported by Public Health Service Research Grants No. CA-10612-01 to No. CA-10612-04 from the National Cancer Institute, and was presented in part at the American Chemical Society Meeting, Washington, D.C., September 1971. We are also grateful to the National Science Foundation for financial assistance (Grant numbers GB-4939 and GB-6979) used in obtaining the Atlas CH-4B and SM-1B mass spectrometers employed in this study. 相似文献
85.
86.
Ravikumar B Vacher C Berger Z Davies JE Luo S Oroz LG Scaravilli F Easton DF Duden R O'Kane CJ Rubinsztein DC 《Nature genetics》2004,36(6):585-595
Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates. Here we show that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains. Sequestration of mTOR impairs its kinase activity and induces autophagy, a key clearance pathway for mutant huntingtin fragments. This protects against polyglutamine toxicity, as the specific mTOR inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell models of Huntington disease, and inhibition of autophagy has the converse effects. Furthermore, rapamycin protects against neurodegeneration in a fly model of Huntington disease, and the rapamycin analog CCI-779 improved performance on four different behavioral tasks and decreased aggregate formation in a mouse model of Huntington disease. Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease. 相似文献
87.
88.
Soderberg AM Kulkarni SR Berger E Fox DW Sako M Frail DA Gal-Yam A Moon DS Cenko SB Yost SA Phillips MM Persson SE Freedman WL Wyatt P Jayawardhana R Paulson D 《Nature》2004,430(7000):648-650
Over the six years since the discovery of the gamma-ray burst GRB 980425, which was associated with the nearby (distance approximately 40 Mpc) supernova 1998bw, astronomers have debated fiercely the nature of this event. Relative to bursts located at cosmological distance (redshift z approximately 1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed that the explosion was sub-energetic by a factor of 10. Here we report observations of the radio and X-ray afterglow of the recent GRB 031203 (refs 5-7), which has a redshift of z = 0.105. We demonstrate that it too is sub-energetic which, when taken together with the low gamma-ray luminosity, suggests that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. We expect intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRB 031203 and 980425) to reveal a large population of such events. 相似文献
89.
90.
p53 is regulated by the lysine demethylase LSD1 总被引:1,自引:0,他引:1
Huang J Sengupta R Espejo AB Lee MG Dorsey JA Richter M Opravil S Shiekhattar R Bedford MT Jenuwein T Berger SL 《Nature》2007,449(7158):105-108