全文获取类型
收费全文 | 3105976篇 |
免费 | 252482篇 |
国内免费 | 76885篇 |
出版年
2021年 | 44791篇 |
2020年 | 33253篇 |
2019年 | 41035篇 |
2018年 | 48110篇 |
2017年 | 42925篇 |
2016年 | 60514篇 |
2015年 | 82385篇 |
2014年 | 100236篇 |
2013年 | 135730篇 |
2012年 | 151261篇 |
2011年 | 151438篇 |
2010年 | 104123篇 |
2009年 | 97531篇 |
2008年 | 129802篇 |
2007年 | 130326篇 |
2006年 | 121904篇 |
2005年 | 114099篇 |
2004年 | 107945篇 |
2003年 | 101543篇 |
2002年 | 96471篇 |
2001年 | 93487篇 |
2000年 | 93988篇 |
1999年 | 78132篇 |
1998年 | 38993篇 |
1997年 | 35794篇 |
1996年 | 32379篇 |
1995年 | 31496篇 |
1994年 | 30341篇 |
1993年 | 28963篇 |
1992年 | 61708篇 |
1991年 | 59403篇 |
1990年 | 57508篇 |
1989年 | 56092篇 |
1988年 | 52496篇 |
1987年 | 49779篇 |
1986年 | 46780篇 |
1985年 | 48123篇 |
1984年 | 41486篇 |
1983年 | 36076篇 |
1982年 | 29795篇 |
1981年 | 27124篇 |
1980年 | 25044篇 |
1979年 | 38346篇 |
1978年 | 30738篇 |
1977年 | 28181篇 |
1976年 | 26326篇 |
1975年 | 28566篇 |
1974年 | 30895篇 |
1973年 | 30094篇 |
1972年 | 26039篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
The differential effect on two hybrid proteins of deletion mutations within the hydrophobic region of the Escherichia coli OmpA signal peptide 总被引:10,自引:0,他引:10
Oligonucleotide-directed site-specific mutagenesis was used to systematically shorten the hydrophobic region within the signal peptide of the Escherichia coli outer membrane protein OmpA. DNA encoding the wild type and mutant OmpA signal peptides were then fused in frame to DNA encoding the mature regions of Staphylococcus aureus nuclease A and TEM beta-lactamase. The ability of these signal peptides to direct processing of the resulting hybrid proteins was dependent on both their length and the protein to which they were fused. Deletion of two or more residues progressively slowed processing of pro-OmpA-nuclease. By contrast, pro-OmpA-beta-lactamase was less sensitive to the length of the hydrophobic region than to the nature of the deleted residue(s). Deletion of an Ala residue tended to reduce processing efficiency of pro-OmpA-beta-lactamase, while deletion of an Ile residue, together with the Ala residue, resulted in improvement. The loss of either 3 or 4 residues abolished processing of both hybrids. These data indicate that both the length as well as the identity of residues in the hydrophobic region are important. The relative importance of these two factors depends on the mature region of the protein being secreted. 相似文献
942.
943.
Relation between D-glucose and L- and D-alanine in the initiation of germination of Bacillus subtilis spore 总被引:1,自引:0,他引:1
The rate of L-alanine-initiated germination of Bacillus subtilis spore was measured by both loss of heat resistance and loss of turbidity, and the effect of glucose on the germination response to a wide range of concentrations of the germinant was analyzed in the presence and absence of D-alanine, an inhibitor. Glucose stimulated L-alanine germination by means of a cooperative effect: glucose increased the affinity of L-alanine by about 3-fold and the rate of germination by about 1.3-fold. However, glucose had little effect on the binding affinity of D-alanine. The apparent binding constant of L-alanine to the spore, which was determined by the next measurable event in the trigger reaction, was 1.2 X 10(-5), that of D-alanine was 6 X 10(-6), and that of glucose was 5 X 10(-5). The relation between the binding site for glucose and those for L- and D-alanine on the spore is discussed. Effect of glucose analogs was also examined. 相似文献
944.
M Sj?lund J Nilsson L Palmberg J Thyberg 《Differentiation; research in biological diversity》1984,27(2):158-162
The effects of prostaglandin E1 (PGE1) on the phenotypic state of enzymatically isolated arterial smooth-muscle cells in primary culture were studied by transmission electron microscopy, thymidine autoradiography, and cell counting. Early in culture (day 0-2), PGE1 stimulated conversion of the cells from contractile (less euchromatic nucleus and cytoplasm dominated by myofilament bundles) to synthetic state (more euchromatic nucleus and cytoplasm dominated by cisternae of rough endoplasmic reticulum and a large Golgi complex). The rate of entrance of the cells into DNA synthesis and mitosis was also increased at this time. Later on (day 3-6), when the majority of the cells had entered synthetic state, PGE1 inhibited DNA synthesis and cellular proliferation. These observations indicate that the effect of prostaglandins on arterial smooth muscle is dual in nature and dependent on the state of differentiation of the cells. 相似文献
945.
946.
Ivana Tonic Wan-Ni Yu Youngku Park Chia-Chen Chen Nissim Hay 《The Journal of biological chemistry》2010,285(31):23790-23798
Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage. 相似文献
947.
Natalia Ermak Bernard Lacour Françoise Goirand Stéphanie Vicca 《Biochemical and biophysical research communications》2010,393(4):783-787
We compared the apoptotic mechanism involved in U937 human monocytic cell line in presence of oxidized low-density lipoproteins (oxLDL) obtained after treatment with hypochlorous acid (HOCl) or copper (Cu).Both types of oxLDL induced U937 apoptotic cell death via the mitochondrial pathway. In contrast to HOCl-oxLDL, Cu-oxLDL induced apoptosis via a caspase-independent mechanism, with no activation of pro-caspase-3, but via the release of apoptosis inducing factor (AIF) from mitochondria.The apoptotic program of the monocyte differs depending on the mode of LDL oxidation, based on differences in the oxidatively modified components of the two oxLDL types. 相似文献
948.
Sandrine Poncet Armelle Delecluse Guido Anello ré Klier Georges Rapoport 《FEMS microbiology letters》1994,117(1):91-95
Abstract The genes encoding the CryIVB and CryIVD crystal polypeptides of B. thuringiensis subsp. israelensis were cloned indepently on a stable shuttle vector, and transfered into B. sphaericus 2297. Recombinant cells expressed the B. thuringiensis toxins during sporulation and were shown to be toxic to Aedes aegypti fourth instar larvae, whereas the parental strain was not. 相似文献
949.
950.