全文获取类型
收费全文 | 5053篇 |
免费 | 368篇 |
国内免费 | 3篇 |
出版年
2024年 | 4篇 |
2023年 | 19篇 |
2022年 | 60篇 |
2021年 | 92篇 |
2020年 | 75篇 |
2019年 | 97篇 |
2018年 | 144篇 |
2017年 | 107篇 |
2016年 | 176篇 |
2015年 | 257篇 |
2014年 | 330篇 |
2013年 | 359篇 |
2012年 | 463篇 |
2011年 | 449篇 |
2010年 | 274篇 |
2009年 | 249篇 |
2008年 | 317篇 |
2007年 | 315篇 |
2006年 | 248篇 |
2005年 | 233篇 |
2004年 | 251篇 |
2003年 | 193篇 |
2002年 | 164篇 |
2001年 | 102篇 |
2000年 | 104篇 |
1999年 | 68篇 |
1998年 | 26篇 |
1997年 | 26篇 |
1996年 | 20篇 |
1995年 | 18篇 |
1994年 | 15篇 |
1993年 | 11篇 |
1992年 | 19篇 |
1991年 | 24篇 |
1990年 | 18篇 |
1989年 | 10篇 |
1988年 | 13篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1982年 | 5篇 |
1980年 | 5篇 |
1978年 | 3篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1967年 | 3篇 |
排序方式: 共有5424条查询结果,搜索用时 437 毫秒
181.
182.
Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18 总被引:12,自引:0,他引:12
183.
Choi KS Jun HS Kim HN Park HJ Eom YW Noh HL Kwon H Kim HM Yoon JW 《Journal of virology》2001,75(4):1949-1957
Soluble mediators such as interleukin-1beta, tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) produced from activated macrophages play an important role in the destruction of pancreatic beta cells in mice infected with a low dose of the D variant of encephalomyocarditis (EMC-D) virus. The tyrosine kinase signaling pathway was shown to be involved in EMC-D virus-induced activation of macrophages. This investigation was initiated to determine whether the Src family of kinases plays a role in the activation of macrophages, subsequently resulting in the destruction of beta cells, in mice infected with a low dose of EMC-D virus. We examined the activation of p59/p56(Hck), p55(Fgr), and p56/p53(Lyn) in macrophages from DBA/2 mice infected with the virus. We found that p59/p56(Hck) showed a marked increase in both autophosphorylation and kinase activity at 48 h after infection, whereas p55(Fgr) and p56/p53(Lyn) did not. The p59/p56(Hck) activity was closely correlated with the tyrosine phosphorylation level of Vav. Treatment of EMC-D virus-infected mice with the Src kinase inhibitor, PP2, resulted in the inhibition of p59/p56(Hck) activity and almost complete inhibition of the production of TNF-alpha and iNOS in macrophages and the subsequent prevention of diabetes in mice. On the basis of these observations, we conclude that the Src kinase, p59/p56(Hck), plays an important role in the activation of macrophages and the subsequent production of TNF-alpha and nitric oxide, leading to the destruction of pancreatic beta cells, which results in the development of diabetes in mice infected with a low dose of EMC-D virus. 相似文献
184.
Leuconostoc sp. J2, isolated from naturally fermented Kimchi, produced a bacteriocin which was named leuconocin J. This bacteriocin exhibited an inhibitory activity against several lactic acid bacteria and some food-borne pathogens. The antimicrobial substance was secreted into the medium during the late log phase. It appears to be proteinaceous since its activity was completely inactivated by a range of proteolytic enzymes, and it was also relatively heat-stable. The bacteriocin was partially purified by ammonium sulphate precipitation, following dialysis. The apparent molecular mass of partially purified bacteriocin, as indicated by activity detection after Tricine-SDS-PAGE, was 2.5-3.5 kDa. Leuconostoc sp. J2 plasmid DNA digested by EcoRI was cloned into pUC118 and transformed into Escherichia coli DH5 alpha. Phenotypic expression of the bacteriocin production was detected in transformants harboring pULBJ5.5. Finally, Southern blotting with the 2.3 kb insert as a probe against plasmid digests of Leuconostoc sp. J2 revealed that the cloned foreign DNA originated from Leuconostoc sp. J2. 相似文献
185.
186.
We have determined the full sequence of the ribosomal DNA intergenic spacer (IGS) of the swimming crab, Charybdis japonica, by long PCR for the first time in crustacean decapods. The IGS is 5376 bp long and contains two nonrepetitive regions separated
by one long repetitive region, which is composed mainly of four subrepeats (subrepeats I, II, III, and IV). Subrepeat I contains
nine copies of a 60-bp repeat unit, in which two similar repeat types (60 bp-a and 60 bp-b) occur alternatively. Subrepeat
II consists of nine successive repeat units with a consensus sequence length of 142 bp. Subrepeat III consists of seven copies
of another 60-bp repeat unit (60 bp-c) whose sequence is complementary to that of subrepeat I. Immediately downstream of subrepeat
III is subrepeat IV, consisting of three copies of a 391-bp repeat unit. Based on comparative analysis among the subrepeats
and repeat units, a possible evolutionary process responsible for the formation of the repetitive region is inferred, which
involves the duplication of a 60-bp subrepeat unit (60 bp-c) as a prototype.
Received: 13 April 1999 / Accepted: 2 August 1999 相似文献
187.
Ryu JR Jin BS Suh MJ Yoo YS Yoon SH Woo ER Yu YG 《Biochemical and biophysical research communications》1999,265(3):625-629
Peptides derived from gp41 effectively block the gp41-mediated cell fusion or HIV infection. A 36-mer (naDP178), 51-mer (C51) and 27-mer peptide (C27) from the membrane proximal region of gp41 have been examined their interaction modes with the coiled-coil motif of gp41 presented in thioredoxin (Trx-N) or the bacterially expressed ectodomain of gp41 (Ec-gp41ec). All of these peptides effectively inhibited the gp41-mediated membrane fusion, however, they showed distinct interaction modes with Ec-gp41ec or Trx-N. C51 peptide bound tightly to Trx-N, and it increased the solubility of Ec-gp41ec. naDP178 showed very weak binding affinity to Trx-N, however, it effectively solubilized Ec-gp41ec. In contrast, C27 peptide showed significant binding to Trx-N; however, it did not affect the solubility of Ec-gp41ec. These interaction modes of C-peptides were assumed to be related to their different inhibitory mechanism against gp41-mediated cell fusion. 相似文献
188.
Effects of dopamine on the membrane permeability transition, thioredoxin reductase activity, production of free radicals and oxidation of sulfhydryl groups in brain mitochondria and the Ca2+ uptake by Na+-Ca2+ exchange and sulfhydryl oxidation in brain synaptosomes were examined. The brain mitochondrial swelling and the fall of transmembrane potential were altered by pretreatment of dopamine in a dose dependent manner. Depressive effect of dopamine on mitochondrial swelling was reversed by 10 g/ml catalase, and 10 mM DMSO. The activities of thioredoxin reductase in intact or disrupted mitochondria were decreased by dopamine (1-100 M), 25 M Zn2+ and 50 M Mn2+. Dopamine-inhibited enzyme activity was reversed by 10 g/ml SOD and 10 g/ml catalase. Pretreatment of dopamine decreased Ca2+ transport in synaptosomes, which was restored by 10 g/ml SOD and 10 mM DMSO. Dopamine (1-100 M) in the medium containing mitochondria produced superoxide anion and hydrogen peroxide, while its effect on nitrite production was very weak. The oxidation of sulfhydryl groups in mitochondria and synaptosomes were enhanced by dopamine with increasing incubation times. Results suggest that dopamine could modulate membrane permeability in mitochondria and calcium transport at nerve terminals, which may be ascribed to the action of free radicals and the loss of reduced sulfhydryl groups. 相似文献
189.
Lee Gap Ryol Kim Se Nyun Noguchi Kohei Park Sang Dai Hong Seung Hwan Cho-Chung Yoon S. 《Molecular and cellular biochemistry》1999,195(1-2):77-86
Expression of the RI regulatory subunit of protein kinase A type I is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. Ala99 (the pseudophosphorylation site) of human RI was replaced with Ser (RI-p) for the structure-function analysis of RI. MCF-7 hormone- dependent breast cancer cells were transfected with an expression vector for the wild-type RI or mutant RI-p. Overexpression of RI-P resulted in suppression of protein kinase A type II, the isozyme of type I kinase, production of kinase exhibiting reduced cAMP activation, and inhibition of cell growth showing an increase in G0/G1 phase of the cell cycle and apoptosis. The wild-type RI overexpression had no effect on protein kinase A isozyme distribution or cell growth. Overexpression of protein kinase A type II regulatory subunit, RII, suppressed RI and protein kinase A type I and inhibited cell growth. These results show that the growth of hormone-dependent breast cancer cells is dependent on the functional protein kinase A type I. 相似文献
190.
Photosynthetic eukaryotes unite: endosymbiosis connects the dots 总被引:15,自引:0,他引:15
Bhattacharya D Yoon HS Hackett JD 《BioEssays : news and reviews in molecular, cellular and developmental biology》2004,26(1):50-60
The photosynthetic organelle of algae and plants (the plastid) traces its origin to a primary endosymbiotic event in which a previously non-photosynthetic protist engulfed and enslaved a cyanobacterium. This eukaryote then gave rise to the red, green and glaucophyte algae. However, many algal lineages, such as the chlorophyll c-containing chromists, have a more complicated evolutionary history involving a secondary endosymbiotic event, in which a protist engulfed an existing eukaryotic alga (in this case, a red alga). Chromists such as diatoms and kelps then rose to great importance in aquatic habitats. Another algal group, the dinoflagellates, has undergone tertiary (engulfment of a secondary plastid) and even quaternary endosymbioses. In this review, we examine algal diversity and show endosymbiosis to be a major force in algal evolution. This area of research has advanced rapidly and long-standing issues such as the chromalveolate hypothesis and the extent of endosymbiotic gene transfer have recently been clarified. 相似文献