全文获取类型
收费全文 | 1793篇 |
免费 | 115篇 |
国内免费 | 1篇 |
专业分类
1909篇 |
出版年
2022年 | 8篇 |
2021年 | 22篇 |
2020年 | 19篇 |
2019年 | 19篇 |
2018年 | 26篇 |
2017年 | 19篇 |
2016年 | 30篇 |
2015年 | 40篇 |
2014年 | 53篇 |
2013年 | 95篇 |
2012年 | 126篇 |
2011年 | 109篇 |
2010年 | 73篇 |
2009年 | 70篇 |
2008年 | 116篇 |
2007年 | 116篇 |
2006年 | 112篇 |
2005年 | 108篇 |
2004年 | 105篇 |
2003年 | 112篇 |
2002年 | 104篇 |
2001年 | 43篇 |
2000年 | 35篇 |
1999年 | 37篇 |
1998年 | 38篇 |
1997年 | 13篇 |
1996年 | 21篇 |
1995年 | 16篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 22篇 |
1991年 | 27篇 |
1990年 | 18篇 |
1989年 | 10篇 |
1988年 | 19篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 6篇 |
1983年 | 11篇 |
1982年 | 8篇 |
1981年 | 12篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有1909条查询结果,搜索用时 15 毫秒
1.
Hisao Tsukamoto Yoshihiro Kubo David L. Farrens Mitsumasa Koyanagi Akihisa Terakita Yuji Furutani 《The Journal of biological chemistry》2015,290(45):27176-27187
Melanopsins play a key role in non-visual photoreception in mammals. Their close phylogenetic relationship to the photopigments in invertebrate visual cells suggests they have evolved to acquire molecular characteristics that are more suited for their non-visual functions. Here we set out to identify such characteristics by comparing the molecular properties of mammalian melanopsin to those of invertebrate melanopsin and visual pigment. Our data show that the Schiff base linking the chromophore retinal to the protein is more susceptive to spontaneous cleavage in mammalian melanopsins. We also find this stability is highly diversified between mammalian species, being particularly unstable for human melanopsin. Through mutagenesis analyses, we find that this diversified stability is mainly due to parallel amino acid substitutions in extracellular regions. We propose that the different stability of the retinal attachment in melanopsins may contribute to functional tuning of non-visual photoreception in mammals. 相似文献
2.
Toshiyuki Hamaoka Yasuyuki Takai Atsushi Kosugi Yumiko Mizushima Junko Shima Tsuneo Kusama Hiromi Fujiwara 《Cancer immunology, immunotherapy : CII》1985,20(3):183-188
Summary A new haptenic compound, a muramyl dipeptide (MDP) derivative (designated as L4-MDP-ONB) cross-reactive with Bacillus Calmette Guerin (BCG) was synthesized. The cross-reactivity of L4-MDP hapten to BCG was demonstrated from the following evidence; (a) lymph node cells from BCG-primed C3H/HeN mice exhibited appreciable L4-MDP-specific proliferative responses to the in vitro stimulation of L4-MDP-modified syngeneic cells (L4-MDP-self); (b) inoculation of L4-MDP-self into footpads of BCG-primed C3H/HeN mice elicited ample delayed type-hypersensitivity (DTH) responses in vivo as measured by footpad swelling; and (c) BCG-primed mice contained L4-MDP-reactive helper T cell activity which functions to augment the generation of effector T cell responses to cell surface antigens. This crossreactivity between L4-MDP hapten and BCG as measured by the helper T cell activity was applied to enhanced induction of tumor-specific immunity. When BCG-primed C3H/HeN mice were immunized with L4-MDP-modified syngeneic X5563 tumor cells, these mice could generate augmented tumor-specific in vivo protective (tumor neutralizing) immunity as well as in vitro cytotoxic T cell responses. These results indicate the effectiveness of L4-MDP hapten in augmenting tumor-specific immunity. The present approach is discussed in the context of potential advantages of this new hapten for its future application to clinical tumor systems. 相似文献
3.
4.
Michael F. Seldin Lawrence A. D'Hoostelaere Alfred D. Steinberg Yumiko Saga Herbert C. Morse III 《Immunogenetics》1987,26(1-2):74-78
Allelic variants of Ly-5 in inbred commensal and other natural populations of mice were analyzed by patterns of restriction fragment length polymorphisms (RFLP) and Southern hybridization using an Ly-5 cDNA probe and by cell-surface staining with a panel of antibodies directed against polymorphic and nonpolymorphic Ly-5 determinants. New Ly-5 alleles were defined by RFLPs generated by both Eco RI and Bam HI restriction enzyme digests. The Mus musculus subspecies and other species within the genus Mus showed a strong correlation between allelic variants defined by restriction enzymes and serologic specificities. The data also suggest the conservation of the Ly-5 gene throughout the genus Mus. 相似文献
5.
Thymidylate synthetase (EC 2.1.1.45) from rat regenerating liver has been purified over 5000-fold to apparent homogeneity by a procedure involving two affinity methods. Molecular weight of the native enzyme was found to be about 68,000, as determined by gel filtration. Electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate yielded a single band of molecular weight of 35,000, suggesting that thymidylate synthetase is a dimer of very similar or identical subunits. The Michaelis constants for deoxyuridylate (dUMP) and (+/-)L-5,10-methylenetetrahydrofolate are 6.8 microM and 65 microM, respectively. Reaction kinetics and product inhibition studies reveal the enzymatic mechanism to be ordered sequential. 5-Fluoro-dUMP, halogenated analog of the nucleotide substrate is a competitive inhibitor of the enzyme, with an apparent Ki value of 5 nM. Amethopterin, analog of the cofactor is also a competitive inhibitor with an apparent Ki value of 23 microM. 相似文献
6.
The increases in the activities of hepatic thymidylate synthetase and thymidine kinase were significantly suppressed at 24 h after 70% partial hepatectomy in rats which had been administered a microtubule disrupter, colchicine or vincristine. The decrease of these enzymic activities was accompanied by a reduction of DNA content in 24 h regenerating liver. The immunoblotting assay showed that the depression of the thymidylate synthetase activity by the injection of colchicine or vincristine was due to the decrease of the enzyme protein. These results indicate that colchicine and vincristine inhibit the DNA synthesis during liver regeneration by inhibiting the induction of the key enzyme in DNA synthesis. 相似文献
7.
8.
Yasuhiko Asada Yoshio Kimura Masaaki Kuwahara Akira Tsukamoto Kazuo Koide Atsuhiro Oka Mitsuru Takanami 《Applied microbiology and biotechnology》1988,29(5):469-473
Summary A ligninase gene has been cloned from a Phanerochaete chrysosporium genomic DNA library. Nucleotide sequencing of the gene has revealed that the ligninase structural gene contains 1116 bp of the protein-encoding sequence, of which 84 bp encode the signal peptide. The protein-encoding sequence is interrupted by eight introns which conform to the universal G-T/A-G splicing rule observed for the 3 and 5 intron boundaries. The putative eukaryotic regulatory sequences, i.e. CAAT and TATA box-like sequences, are present in the 5 flanking region. 相似文献
9.
Masao Ohkuchi Masami Tsukamoto Toru Yokoyama Masami Shiratsuchi Yasumi Uchida 《Prostaglandins & other lipid mediators》1988,36(6)
To isolate and identify the plasma factor which stimulates prostaglandin I 2 production by rat aortic ring, a human plasma fraction which showed a major stimulating activity on prostaglandin I 2 production was purified by ultrafiltrate, Sephadex G-10 gel filtration and QAE-Sephadex column chromatography. The purified plasma factor was identified as acid by its ultraviolet and infrared absorption spectroscopy, and 1H nmr and 13C nmr spectroscopy. The stimulating activity of the purified plasma factor and that of authentic uric acid coincided with each other. The stimulating potency of uric acid at its physiological concentration in human plasma (about 50 μg/ml) was half of the deproteinized human plasma, and was about 30 fold stronger than that of L-tryptophan, a cofactor of prostaglandin hyperoxidase. 相似文献
10.