全文获取类型
收费全文 | 4072篇 |
免费 | 319篇 |
国内免费 | 2篇 |
出版年
2022年 | 14篇 |
2021年 | 44篇 |
2020年 | 24篇 |
2019年 | 22篇 |
2018年 | 44篇 |
2017年 | 37篇 |
2016年 | 72篇 |
2015年 | 138篇 |
2014年 | 153篇 |
2013年 | 280篇 |
2012年 | 221篇 |
2011年 | 252篇 |
2010年 | 154篇 |
2009年 | 163篇 |
2008年 | 230篇 |
2007年 | 217篇 |
2006年 | 245篇 |
2005年 | 253篇 |
2004年 | 279篇 |
2003年 | 247篇 |
2002年 | 239篇 |
2001年 | 68篇 |
2000年 | 70篇 |
1999年 | 77篇 |
1998年 | 67篇 |
1997年 | 49篇 |
1996年 | 34篇 |
1995年 | 33篇 |
1994年 | 41篇 |
1993年 | 38篇 |
1992年 | 55篇 |
1991年 | 40篇 |
1990年 | 51篇 |
1989年 | 38篇 |
1988年 | 51篇 |
1987年 | 31篇 |
1986年 | 29篇 |
1985年 | 28篇 |
1984年 | 17篇 |
1983年 | 15篇 |
1982年 | 26篇 |
1981年 | 19篇 |
1979年 | 25篇 |
1978年 | 21篇 |
1977年 | 16篇 |
1976年 | 12篇 |
1975年 | 13篇 |
1974年 | 14篇 |
1971年 | 12篇 |
1968年 | 15篇 |
排序方式: 共有4393条查询结果,搜索用时 62 毫秒
21.
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
22.
Mizuo Takashima Masatoshi Takita Asami Umino Toru Nishikawa Hiroshi Mitsushio Kiyohisa Takahashi 《Neurochemistry international》1992,20(4):583-589
We investigated the effects of interruption of the impulse flow in the habenulopeduncular pathways by local infusion of tetrodotoxin on the acetylcholine and choline content in selected dopamine rich regions in the forebrain and midbrain in rats. The tetrodotoxin infusion caused a marked increase in acetylcholine content in the medial frontal cortex, striatum and ventral tegmental area+interpeduncular nucleus, but not in the limbic area or the substantia nigra, whereas choline content was reduced only in both the striatum and ventral tegmental area+interpeduncular nucleus. There was an increase in 3,4-dihydroxyphenylacetic acid content in the striatum after the manipulation. These findings suggest that the dorsal diencephalic conduction system may be involved in the integration of the activity of cholinergic neurons in the forebrain and midbrain regions and striatal dopanine neurons may play a role in the modulation of cholinergic neurons. 相似文献
23.
Participation of glutamic acid 23 of T4 endonuclease V in the beta-elimination reaction of an abasic site in a synthetic duplex DNA. 下载免费PDF全文
T4 endonuclease V catalyzes the hydrolysis of the glycosyl bond of a thymine dimer in a DNA duplex and the cleavage of the 3'-phosphate by beta-elimination. We have previously identified a catalytic site for the first reaction (pyrimidine dimer-glycosylase activity) by systematic mutagenesis (Doi et al. Proc. Natl. Acad. Sci. USA 1992 in press) and by x-ray crystallography (Morikawa et al. Science, 256: 523-526, 1992). The results showed that replacement of Glu23 with either glutamine or aspartic acid completely abolished the glycosylase activity. We describe the investigation of the second reaction (apurinic/apyrimidinic endonuclease activity), using twenty two mutants of T4 endonuclease V plus a DNA mini duplex containing an abasic site. Replacement of Glu23 by glutamine abolished the second reaction, but replacement with aspartic acid did not. The pH optima of the mutant (23 Asp) and the wild type were found to be 5.0 and 5.5, respectively. We conclude that the carboxylate anion in position 23 may act as a general base in the beta-elimination reaction of the endonuclease. 相似文献
24.
Antipsychotics represent high affinity for sigma receptors and sigma-like drugs often have the psychotomimetic properties. Besides, the receptors are unevenly distributed in human brain. These findings suggest that sigma receptors might be involved in the pathophysiology of schizophrenia. Sigma receptors in rat and human brain were measured with [3H]-1, 3, di-o-tolylguanidine (DTG) and non-specific binding of [3H]DTG was determined in the presence of 10–5M haloperidol. Monovalent and divalent cations strongly inhibited [3H]DTG binding. Glutamate, aspartate and glycine also decreased the binding to human cerebral membranes. With post-mortem brain samples from 12 schizophrenics and 10 controls, sigma receptors were measured in 17 areas of cerebral cortex. Sigma receptors binding showed the regional differences in the cortex, but no significant differences between schizophrenics and controls were observed except the superior parietal cortex where the binding significantly increased in the schizophrenic group. These results suggest that sigma receptors in cerebral cortices might not be directly concerned with the pathophysiological role in schizophrenia.Dedicated to Dr. Morris Aprison. Received too late for publication in special issue. 相似文献
25.
26.
Conformational dynamics of DNA affected by intercalation and minor groove binding: direct observation of large DNA. 总被引:1,自引:0,他引:1
Y Matsuzawa K Minagawa K Yoshikawa M Matsumoto M Doi 《Nucleic acids symposium series》1991,(25):131-132
Using fluorescence microscopy, we have observed moving DNA molecules in solution and analyzed the "higher-order" structure in a quantitative manner. It was found that EB (ethidium bromide), an intercalator, has the effect to increase the persistent length. In other words, EB expands DNA. Whereas, DAPI (4',6-diamidino-2-phenylindole), a minor groove binding drug, decreases the persistent length. It is demonstrated that the direct observation of DNA molecules with fluorescence microscopy is quite useful to study the interaction of various chemical compounds with DNA molecules. 相似文献
27.
Analyses of intramolecular disulfide bonds in proteins by polyacrylamide gel electrophoresis following two-step alkylation 总被引:1,自引:0,他引:1
A method that makes use of polyacrylamide gel electrophoresis was developed for the analysis of intramolecular disulfide bonds in proteins. Proteins with different numbers of cleaved disulfide bonds are alkylated with iodoacetic acid or iodoacetamide as the first step. The disulfide bonds remaining were reduced by excess dithiothreitol, and the newly generated free sulfhydryl groups were alkylated with the reagent not yet used (iodoacetamide, iodoacetic acid, or vinyl-pyridine) as the second step. This treatment made it possible for lysozyme (Mr, 14,000; 4 disulfides), the N-terminal half-molecule of conalbumin (Mr, 36,000; 6 disulfides), the C-terminal half-molecule of conalbumin (Mr, 40,000; 9 disulfides), and whole conalbumin (Mr, 78,000; 15 disulfides) to be separated by acid-urea polyacrylamide gel electrophoresis into distinct bands depending on the number of disulfide bonds cleaved. The method allowed us to determine the total number of disulfide bonds in native proteins and to assess the cleaved levels of disulfide bonds in partially reduced proteins. Two-step alkylation used in combination with radioautography was especially useful for the analysis of disulfide bonds in proteins synthesized in complex biological systems. 相似文献
28.
Several physicochemical parameters of ovalbumin were examined at acid pH. The intrinsic viscosity and far UV-CD spectrum at pH 2 did not differ from those at pH 7. But the near UV-CD spectrum, difference absorption spectrum around 250-320 nm, and fluorescence spectrum showed micro-environmental changes around the aromatic amino acid residues in acid solution. The reactivity of one of the four sulfhydryl groups with 2,2'-dithiodipyridine increased at pH below 5. The rate of denaturation by urea and that of surface tension decay were high in the low pH range. We concluded that at low pH (around 2), ovalbumin molecules kept their native globular conformation, but that their chain flexibility increased and they were very susceptible to denaturation. This state might be equivalent to the molten-globule state observed with some globular proteins in acidic region. 相似文献
29.
T Ishida K Kamiichi A Kuwahara M Doi M Inoue 《Biochemical and biophysical research communications》1986,136(1):294-299
The crystal structure of title complex has been analyzed by X-ray diffraction method as a model for elucidating the possible interaction between the phenylalanyl residue of proteins and the N7-protonated or methylated guanine base of nucleic acids. The guanine base is associated with the benzene ring of phenylalanine by stacking interaction, and further connected with the carboxyl group by the formation of a pair of hydrogen bonds. These two interaction modes are suggested to be responsible for the specific recognition of base sequence by protein. 相似文献
30.
Translational coupling in Escherichia coli of a heterologous Bacillus subtilis-Escherichia coli gene fusion. 总被引:1,自引:0,他引:1 下载免费PDF全文
The efficient expression in Escherichia coli of the Tn9-derived chloramphenicol acetyltransferase (EC 2.3.1.28) gene fused distal to the promoter and N terminus of the Bacillus subtilis aprA gene was dependent on the initiation of translation from the ribosome-binding site in the aprA gene. 相似文献