全文获取类型
收费全文 | 2101篇 |
免费 | 240篇 |
出版年
2021年 | 25篇 |
2020年 | 21篇 |
2019年 | 24篇 |
2018年 | 25篇 |
2017年 | 24篇 |
2016年 | 46篇 |
2015年 | 65篇 |
2014年 | 66篇 |
2013年 | 78篇 |
2012年 | 90篇 |
2011年 | 108篇 |
2010年 | 65篇 |
2009年 | 63篇 |
2008年 | 90篇 |
2007年 | 89篇 |
2006年 | 68篇 |
2005年 | 81篇 |
2004年 | 90篇 |
2003年 | 75篇 |
2002年 | 77篇 |
2001年 | 50篇 |
2000年 | 45篇 |
1999年 | 49篇 |
1998年 | 35篇 |
1997年 | 19篇 |
1996年 | 20篇 |
1994年 | 21篇 |
1993年 | 24篇 |
1992年 | 31篇 |
1991年 | 39篇 |
1990年 | 25篇 |
1989年 | 24篇 |
1988年 | 35篇 |
1987年 | 20篇 |
1985年 | 24篇 |
1984年 | 21篇 |
1983年 | 26篇 |
1981年 | 19篇 |
1980年 | 18篇 |
1978年 | 36篇 |
1977年 | 21篇 |
1976年 | 27篇 |
1975年 | 18篇 |
1974年 | 32篇 |
1973年 | 19篇 |
1972年 | 17篇 |
1971年 | 19篇 |
1969年 | 17篇 |
1967年 | 19篇 |
1966年 | 17篇 |
排序方式: 共有2341条查询结果,搜索用时 250 毫秒
121.
122.
A full length (192 amino acids) uracil-DNA glycosylase (TMUDG) has been expressed and purified from the extreme thermophile Thermotoga maritima. This protein is active up to 85 degrees C. The enzyme is product inhibited by abasic sites in DNA and weakly inhibited by uracil. TMUDG was originally cloned from an ORF which encoded a protein of 185 amino acids. This shorter protein was stable up to 70-75 degrees C and it seemed unusual that this enzyme had an optimal activity temperature below the growth temperature of the organism (80-90 degrees C). Following the publication of the complete genomic sequence of T. maritima, it was shown that the gene contains an additional seven amino acids (LYTREEL) at the N-terminal end of the protein. It is suggested that these seven residues are important in maintaining proper protein folding that results in increased temperature stability. We have also demonstrated that TMUDG can substitute for the Escherichia coli uracil-DNA glycosylase and initiate base excision repair using a closed circular DNA substrate containing a unique U:G base pair. 相似文献
123.
124.
Purification and characterization of Thermotoga maritima endonuclease IV, a thermostable apurinic/apyrimidinic endonuclease and 3'-repair diesterase
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Haas BJ Sandigursky M Tainer JA Franklin WA Cunningham RP 《Journal of bacteriology》1999,181(9):2834-2839
An endonuclease IV homolog was identified as the product of a conceptual open reading frame in the genome of the hyperthermophilic bacterium Thermotoga maritima. The T. maritima endonuclease IV gene encodes a 287-amino-acid protein with 32% sequence identity to Escherichia coli endonuclease IV. The gene was cloned, and the expressed protein was purified and shown to have enzymatic activities that are characteristic of the endonuclease IV family of DNA repair enzymes, including apurinic/apyrimidinic endonuclease activity and repair activities on 3'-phosphates, 3'-phosphoglycolates, and 3'-trans-4-hydroxy-2-pentenal-5-phosphates. The T. maritima enzyme exhibits enzyme activity at both low and high temperatures. Circular dichroism spectroscopy indicates that T. maritima endonuclease IV has secondary structure similar to that of E. coli endonuclease IV and that the T. maritima endonuclease IV structure is more stable than E. coli endonuclease IV by almost 20 degrees C, beginning to rapidly denature only at temperatures approaching 90 degrees C. The presence of this enzyme, which is part of the DNA base excision repair pathway, suggests that thermophiles use a mechanism similar to that used by mesophiles to deal with the large number of abasic sites that arise in their chromosomes due to the increased rates of DNA damage at elevated temperatures. 相似文献
125.
The Distribution of Microbial Communities in Anaerobic and Aerobic Zones of a Shallow Coastal Plain Aquifer 总被引:2,自引:0,他引:2
Abstract
Randomly amplified polymorphic DNA (RAPD) fingerprinting was used to determine the genetic similarity of whole-community DNA
extracts from unattached microorganisms in several groundwater wells. The study site was a shallow coastal plain aquifer on
the Eastern Shore of Virginia that contains distinct regions of anaerobic and aerobic groundwater. Several wells in each region
were sampled, and principal component and cluster analyses showed a clear separation of the microbial communities from the
two chemical zones of the aquifer. Within these zones, there was no relationship between the genetic relatedness of a pair
of communities and their spatial separation. Two additional sets of samples were taken at later times, and the same clear
separation between communities in the different zones of the aquifer was observed. The specific relationships between wells
within each zone changed over time, however, and the magnitude and direction of these changes corresponded to concurrent changes
in the groundwater chemistry at each well. Together, these results suggest that local variation in groundwater chemistry can
support genetically distinct microbial communities, and that the composition of the microbial communities can follow seasonal
fluctuations in groundwater chemistry.
Received: 25 May 1999; Accepted: 4 August 1999; Online Publication: 9 December 1999 相似文献
126.
Srikanth Sampathkumar Franklin Christopher C. Duke Richard C. Kraft Andrew S. 《Molecular and cellular biochemistry》1999,199(1-2):169-178
Recent studies have suggested that MAP kinase phosphatase 1 (MKP-1) is overexpressed in prostate cancer. To evaluate the role of MKP-1 in regulating cell death and tumor growth in prostate cancer, MKP-1 was conditionally overexpressed in the human prostate cancer cell line DU145. Overexpression of MKP-1 in DU145 cells blocked activation of stress-activated protein kinase (SAPK/JNK). MKP-1 overexpression in DU-145 cells was also found to inhibit Fas ligand (FasL)-induced apoptosis, as well as block the activation of caspases by Fas engagement. In addition, MKP-1 blocked the activation of apoptosis by transfected MEKK-1 and ASK-1, presumably through its inhibition of the SAPK/JNK family of enzymes. MKP-1 blocked the ability of FasL to induce loss of mitochondrial transmembrane potential (m), suggesting that MKP-1 acts upstream of mitochondrial pro-apoptotic events induced by FasL and that the SAPK/JNK pathway may form the signaling link between Fas receptor and mitochondrial dysfunction. Thus, MKP-1 overexpression in prostate cancer may play a role in promoting prostate carcinogenesis by inhibiting FasL-induced cell death. 相似文献
127.
128.
Botta D Franklin CC White CC Krejsa CM Dabrowski MJ Pierce RH Fausto N Kavanagh TJ 《Free radical biology & medicine》2004,37(5):632-642
Glutathione (GSH) is important in free radical scavenging, maintaining cellular redox status, and regulating cell survival in response to a wide variety of toxicants. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), which is composed of catalytic (GCLC) and modifier (GCLM) subunits. To determine whether increased GSH biosynthetic capacity enhances cellular resistance to tumor necrosis factor-alpha- (TNF-alpha-) induced apoptotic cell death, we have established several mouse liver hepatoma (Hepa-1) cell lines overexpressing GCLC and/or GCLM. Cells overexpressing GCLC alone exhibit modest increases in GCL activity, while cells overexpressing both subunits have large increases in GCL activity. Importantly, cells overexpressing both GCL subunits exhibit increased resistance to TNF-induced apoptosis as judged by a loss of redox potential; mitochondrial membrane potential; translocation of cytochrome c to the cytoplasm; and activation of caspase-3, caspase-8, and caspase-9. Analysis of the effects of TNF on these parameters indicates that maintaining mitochondrial integrity mediates this protective effect in GCL-overexpressing cells. 相似文献
129.
130.
Lieberman DE Krovitz GE Yates FW Devlin M St Claire M 《Journal of human evolution》2004,46(6):655-677
Changes in the technology of food preparation over the last few thousand years (especially cooking, softening, and grinding) are hypothesized to have contributed to smaller facial size in humans because of less growth in response to strains generated by chewing softer, more processed food. While there is considerable comparative evidence to support this idea, most experimental tests of this hypothesis have been on non-human primates or other very prognathic mammals (rodents, swine) raised on hard versus very soft (nearly liquid) diets. Here, we examine facial growth and in vivo strains generated in response to raw/dried foods versus cooked foods in a retrognathic mammal, the rock hyrax (Procavia capensis). The results indicate that the hyrax cranium resembles the non-human primate cranium in having a steep gradient of strains from the occlusal to orbital regions, but differs from most non-anthropoids in being primarily twisted; the hyrax mandible is bent both vertically and laterally. In general, higher strains, as much as two-fold at some sites, are generated by masticating raw versus cooked food. Hyraxes raised on cooked food had significantly less growth (approximately 10%) in the ventral (inferior) and posterior portions of the face, where strains are highest, resembling many of the differences evident between humans raised on highly processed versus less processed diets. The results support the hypothesis that food processing techniques have led to decreased facial growth in the mandibular and maxillary arches in recent human populations. 相似文献