全文获取类型
收费全文 | 118篇 |
免费 | 2篇 |
国内免费 | 3篇 |
专业分类
理论与方法论 | 1篇 |
现状及发展 | 45篇 |
研究方法 | 19篇 |
综合类 | 58篇 |
出版年
2018年 | 1篇 |
2015年 | 3篇 |
2014年 | 1篇 |
2013年 | 2篇 |
2012年 | 10篇 |
2011年 | 8篇 |
2010年 | 7篇 |
2009年 | 1篇 |
2008年 | 10篇 |
2007年 | 4篇 |
2006年 | 5篇 |
2005年 | 7篇 |
2004年 | 5篇 |
2003年 | 8篇 |
2002年 | 5篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1971年 | 2篇 |
1967年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有123条查询结果,搜索用时 337 毫秒
1.
Summary After injection of microspheres into both renal arteries of rats, an irreversible shock syndrome develops, resulting in death within 4–12 h. Ligation of both renal pedicles after injection of microspheres prevents the shock. It is presumed that kininogenases released from the kidneys participate in the pathogenesis of the shock syndrome.These studies were supported in part by the Deutsche Forschungsgemeinschaft within the SFB 90, Cardiovasculäres System. 相似文献
2.
Bernd Kaina Geoffrey P. Margison Markus Christmann 《Cellular and molecular life sciences : CMLS》2010,67(21):3663-3681
O
6-methylguanine-DNA methyltransferase (MGMT) repairs the cancer chemotherapy-relevant DNA adducts, O
6-methylguanine and O
6-chloroethylguanine, induced by methylating and chloroethylating anticancer drugs, respectively. These adducts are cytotoxic,
and given the overwhelming evidence that MGMT is a key factor in resistance, strategies for inactivating MGMT have been pursued.
A number of drugs have been shown to inactivate MGMT in cells, human tumour models and cancer patients, and O
6-benzylguanine and O
6-[4-bromothenyl]guanine have been used in clinical trials. While these agents show no side effects per se, they also inactivate
MGMT in normal tissues and hence exacerbate the toxic side effects of the alkylating drugs, requiring dose reduction. This
might explain why, in any of the reported trials, the outcome has not been improved by their inclusion. It is, however, anticipated
that, with the availability of tumour targeting strategies and hematopoetic stem cell protection, MGMT inactivators hold promise
for enhancing the effectiveness of alkylating agent chemotherapy. 相似文献
3.
Lahaye T Koch T Fröhlich B Fattori M Metz J Griesmaier A Giovanazzi S Pfau T 《Nature》2007,448(7154):672-675
Symmetry-breaking interactions have a crucial role in many areas of physics, ranging from classical ferrofluids to superfluid (3)He and d-wave superconductivity. For superfluid quantum gases, a variety of new physical phenomena arising from the symmetry-breaking interaction between electric or magnetic dipoles are expected. Novel quantum phases in optical lattices, such as chequerboard or supersolid phases, are predicted for dipolar bosons. Dipolar interactions can also enrich considerably the physics of quantum gases with internal degrees of freedom. Arrays of dipolar particles could be used for efficient quantum information processing. Here we report the realization of a chromium Bose-Einstein condensate with strong dipolar interactions. By using a Feshbach resonance, we reduce the usual isotropic contact interaction, such that the anisotropic magnetic dipole-dipole interaction between 52Cr atoms becomes comparable in strength. This induces a change of the aspect ratio of the atom cloud; for strong dipolar interactions, the inversion of ellipticity during expansion (the usual 'smoking gun' evidence for a Bose-Einstein condensate) can be suppressed. These effects are accounted for by taking into account the dipolar interaction in the superfluid hydrodynamic equations governing the dynamics of the gas, in the same way as classical ferrofluids can be described by including dipolar terms in the classical hydrodynamic equations. Our results are a first step in the exploration of the unique properties of quantum ferrofluids. 相似文献
4.
5.
Mackereth CD Madl T Bonnal S Simon B Zanier K Gasch A Rybin V Valcárcel J Sattler M 《Nature》2011,475(7356):408-411
Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins. 相似文献
6.
Holst F Stahl PR Ruiz C Hellwinkel O Jehan Z Wendland M Lebeau A Terracciano L Al-Kuraya K Jänicke F Sauter G Simon R 《Nature genetics》2007,39(5):655-660
Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers. 相似文献
7.
Kalay E Yigit G Aslan Y Brown KE Pohl E Bicknell LS Kayserili H Li Y Tüysüz B Nürnberg G Kiess W Koegl M Baessmann I Buruk K Toraman B Kayipmaz S Kul S Ikbal M Turner DJ Taylor MS Aerts J Scott C Milstein K Dollfus H Wieczorek D Brunner HG Hurles M Jackson AP Rauch A Nürnberg P Karagüzel A Wollnik B 《Nature genetics》2011,43(1):23-26
Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation. 相似文献
8.
Sayer JA Otto EA O'Toole JF Nurnberg G Kennedy MA Becker C Hennies HC Helou J Attanasio M Fausett BV Utsch B Khanna H Liu Y Drummond I Kawakami I Kusakabe T Tsuda M Ma L Lee H Larson RG Allen SJ Wilkinson CJ Nigg EA Shou C Lillo C Williams DS Hoppe B Kemper MJ Neuhaus T Parisi MA Glass IA Petry M Kispert A Gloy J Ganner A Walz G Zhu X Goldman D Nurnberg P Swaroop A Leroux MR Hildebrandt F 《Nature genetics》2006,38(6):674-681
9.
Vesicle fusion following receptor-mediated endocytosis requires a protein active in Golgi transport 总被引:53,自引:0,他引:53
In reconstitution studies N-ethylmaleimide, a sulphydryl alkylating reagent, inhibits both fusion of endocytic vesicles and vesicular transport in the Golgi apparatus. We show here that the same N-ethylmaleimide-sensitive factor that catalyses the vesicle-mediated transport within Golgi stacks is also required for endocytic vesicle fusion. Thus, it is likely that a common mechanism for vesicle fusion exists for both the secretory and endocytic pathways of eukaryotic cells. 相似文献
10.
The extent of linkage disequilibrium in Arabidopsis thaliana. 总被引:20,自引:0,他引:20
Magnus Nordborg Justin O Borevitz Joy Bergelson Charles C Berry Joanne Chory Jenny Hagenblad Martin Kreitman Julin N Maloof Tina Noyes Peter J Oefner Eli A Stahl Detlef Weigel 《Nature genetics》2002,30(2):190-193
Linkage disequilibrium (LD), the nonrandom occurrence of alleles in haplotypes, has long been of interest to population geneticists. Recently, the rapidly increasing availability of genomic polymorphism data has fueled interest in LD as a tool for fine-scale mapping, in particular for human disease loci. The chromosomal extent of LD is crucial in this context, because it determines how dense a map must be for associations to be detected and, conversely, limits how finely loci may be mapped. Arabidopsis thaliana is expected to harbor unusually extensive LD because of its high degree of selfing. Several polymorphism studies have found very strong LD within individual loci, but also evidence of some recombination. Here we investigate the pattern of LD on a genomic scale and show that in global samples, LD decays within approximately 1 cM, or 250 kb. We also show that LD in local populations may be much stronger than that of global populations, presumably as a result of founder events. The combination of a relatively high level of polymorphism and extensive haplotype structure bodes well for developing a genome-wide LD map in A. thaliana. 相似文献