全文获取类型
收费全文 | 2837篇 |
免费 | 196篇 |
国内免费 | 1篇 |
专业分类
3034篇 |
出版年
2022年 | 23篇 |
2021年 | 37篇 |
2020年 | 15篇 |
2019年 | 32篇 |
2018年 | 47篇 |
2017年 | 44篇 |
2016年 | 56篇 |
2015年 | 73篇 |
2014年 | 108篇 |
2013年 | 146篇 |
2012年 | 169篇 |
2011年 | 186篇 |
2010年 | 111篇 |
2009年 | 99篇 |
2008年 | 178篇 |
2007年 | 187篇 |
2006年 | 147篇 |
2005年 | 139篇 |
2004年 | 155篇 |
2003年 | 134篇 |
2002年 | 112篇 |
2001年 | 74篇 |
2000年 | 68篇 |
1999年 | 49篇 |
1998年 | 31篇 |
1997年 | 32篇 |
1996年 | 30篇 |
1995年 | 26篇 |
1994年 | 22篇 |
1993年 | 18篇 |
1992年 | 41篇 |
1991年 | 48篇 |
1990年 | 42篇 |
1989年 | 30篇 |
1988年 | 38篇 |
1987年 | 31篇 |
1986年 | 22篇 |
1985年 | 20篇 |
1983年 | 15篇 |
1982年 | 13篇 |
1981年 | 10篇 |
1980年 | 15篇 |
1979年 | 14篇 |
1977年 | 13篇 |
1975年 | 12篇 |
1974年 | 14篇 |
1973年 | 15篇 |
1971年 | 10篇 |
1970年 | 16篇 |
1969年 | 13篇 |
排序方式: 共有3034条查询结果,搜索用时 9 毫秒
171.
Conjugated eicosapentaenoic acid (CEPA) and conjugated docosahexaenoic acid (CDHA) with triene structure, isomerized by alkaline treatment, showed intensive cytotoxicity with LD(50) at 12 and 16 microM, respectively, in DLD-1 cells (colorectal adenocarcinoma), while they had no effect on normal human fibroblast cell lines such as MRC-5, TIG-103, and KMS-6 cells. Cytotoxic action of CEPA and CDHA was also demonstrated in other tumor cell lines including HepG2, A549, MCF-7, and MKN-7 cells. alpha-Tocopherol suppressed cytotoxicity of CEPA and CDHA in tumor cells, and the cytotoxicity involved membrane phospholipid peroxidation. CEPA and CDHA induced DNA condensation and fragmentation in DLD-1 cells, indicating the involvement of apoptosis in this cytotoxic mechanism. Furthermore, previous reports have shown that lipid peroxidation product induces cell death, including apoptotic cell death in different cell lines. CEPA and CDHA have been demonstrated in cultured cells to cause cell death via lipid peroxidation and apoptosis in the absence of alpha-tocopherol. 相似文献
172.
Interferon gamma priming is not critical for IL-12 production of murine spleen cells 总被引:2,自引:0,他引:2
Interferon gamma (IFN-gamma) priming is considered to be critical for interleukin 12 (IL-12) production of murine macrophages and human monocytes by lipopolysaccharide (LPS) stimulation. In our present experiments, freshly prepared spleen cells (f-spleen cells) were confirmed not to produce detectable level of IL-12 by LPS stimulation, although they produced significant amount of IL-12 by the stimulation with LPS plus IFN-gamma. However, the stimulation only with LPS induced IL-12 production of spleen cells preincubated in the absence of IFN-gamma. Findings on IL-12 p40 mRNA accumulation were consistent with their IL-12 production. Essentially the same results were obtained using spleen cells from IFN-gamma deficient mice. In the presence of anti-IL-10, f-spleen cells produced IL-12 upon LPS stimulation, indicating that the failure of f-spleen cells in IL-12 production is caused by IL-10 produced by themselves upon LPS stimulation. In addition, f-spleen cells produced IL-12 upon CD40 ligand stimulation, and the production was hardly affected by the presence of IFN-gamma or preincubation. These results indicate that IFN-gamma priming is not critical for IL-12 production of spleen cells stimulated with LPS or CD40 ligand, although IFN-gamma enhances the production, especially, in response to LPS stimulation. 相似文献
173.
To study the signal transduction of cytokinins, we characterized cytokinin-binding proteins (CBPs) isolated from tobacco callus Nicotiana tabacum. Two high-affinity CBPs, CBP1 and CBP2, were isolated from the soluble fraction of tobacco callus BY-2 cells by anion exchange chromatography on a DEAE-cellulose column and affinity chromatography on a benzyladenine (BA)-linked Sepharose 4B column. Cytokinin-binding activity was determined by the equilibrium dialysis method. The degree of purification of CBP1 and CBP2 was 270 and 600-fold, respectively. These proteins had molecular masses of 34 kDa and 26 kDa, and to bind benzyladenine (BA) with dissociation constants (Kd) of 8.9 x 10(-6) M and 1.1 x 10(-6) M, respectively. Binding of BA to CBP2 was inhibited by zeatin and kinetin but not by adenine, adenosine, ATP or IAA. The optimum pH for binding of BA to CBP1 and CBP2 was approximately pH 6.5 and 7.5, respectively. CBP1 showed significant homology (90%) with endochitinase and CBP2 with osmotin-like protein (OLP). These findings and the results of immunoblotting analysis and cytokinin-binding assay of recombinant OLP indicated that CBP2 is OLP, a stress protein. 相似文献
174.
Interaction of Epstein-Barr virus nuclear antigen leader protein (EBNA-LP) with HS1-associated protein X-1: implication of cytoplasmic function of EBNA-LP 下载免费PDF全文
Kawaguchi Y Nakajima K Igarashi M Morita T Tanaka M Suzuki M Yokoyama A Matsuda G Kato K Kanamori M Hirai K 《Journal of virology》2000,74(21):10104-10111
Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) consists of W1W2 repeats and a unique C-terminal Y1Y2 domain and has been suggested to play an important role in EBV-induced transformation. To identify the cellular factors interacting with EBNA-LP, we performed a yeast two-hybrid screen, using EBNA-LP cDNA containing four W1W2 repeats as bait and an EBV-transformed human peripheral blood lymphocyte cDNA library as the source of cellular genes. Our results were as follows. (i) All three cDNAs in positive yeast colonies were found to encode the same cellular protein, HS1-associated protein X-1 (HAX-1), which is localized mainly in the cytoplasm and has been suggested to be involved in the regulation of B-cell signal transduction and apoptosis. (ii) Mutational analysis of EBNA-LP revealed that the association with HAX-1 is mediated by the W1W2 repeat domain. (iii) A purified chimeric protein consisting of glutathione S-transferase fused to EBNA-LP specifically formed complexes with HAX-1 transiently expressed in COS-7 cells. (iv) When EBNA-LP and HAX-1 were coexpressed in COS-7 cells, EBNA-LP was specifically coimmunoprecipitated with HAX-1. (v) Careful cell fractionation experiments of an EBV-infected lymphoblastoid cell line revealed that EBNA-LP is localized in the cytoplasm as well as in the nucleus. (vi) When EBNA-LP containing four W1W2 repeats was expressed in COS-7 cells, EBNA-LP was detected mainly in the nucleus by immunofluorescence assay. Interestingly, when EBNA-LP containing a single W1W2 repeat was expressed in COS-7 cells, EBNA-LP was localized predominantly in the cytoplasm and was colocalized with HAX-1. These results indicate that EBNA-LP is in fact present and may have a significant function in the cytoplasm, possibly by interacting with and affecting the function of HAX-1. 相似文献
175.
176.
Identification of Bach2 as a B-cell-specific partner for small maf proteins that negatively regulate the immunoglobulin heavy chain gene 3'' enhancer. 下载免费PDF全文
A Muto H Hoshino L Madisen N Yanai M Obinata H Karasuyama N Hayashi H Nakauchi M Yamamoto M Groudine K Igarashi 《The EMBO journal》1998,17(19):5734-5743
177.
178.
179.
Yosuke?Shida Kaori?Yamaguchi Mikiko?Nitta Ayana?Nakamura Machiko?Takahashi Shun-ichi?Kidokoro Kazuki?Mori Kosuke?Tashiro Satoru?Kuhara Tomohiko?Matsuzawa Katsuro?Yaoi Yasumitsu?Sakamoto Nobutada?Tanaka Yasushi?Morikawa Wataru?OgasawaraEmail author 《Biotechnology for biofuels》2015,8(1):230
Background
The filamentous fungus Trichoderma reesei (anamorph of Hypocrea jecorina) produces increased cellulase expression when grown on cellulose or its derivatives as a sole carbon source. It has been believed that β-glucosidases of T. reesei not only metabolize cellobiose but also contribute in the production of inducers of cellulase gene expression by their transglycosylation activity. The cellulase hyper-producing mutant PC-3-7 developed in Japan has enhanced cellulase production ability when cellobiose is used as the inducer. The comparative genomics analysis of PC-3-7 and its parent revealed a single-nucleotide mutation within the bgl2 gene encoding intracellular β-glucosidase II (BGLII/Cel1a), giving rise to an amino acid substitution in PC-3-7, which could potentially account for the enhanced cellulase expression when these strains are cultivated on cellulose and cellobiose.Results
To analyze the effects of the BGLII mutation in cellulase induction, we constructed both a bgl2 revertant and a disruptant. Enzymatic analysis of the transformant lysates showed that the strain expressing mutant BGLII exhibited weakened cellobiose hydrolytic activity, but produced some transglycosylation products, suggesting that the SNP in bgl2 strongly diminished cellobiase activity, but did not result in complete loss of function of BGLII. The analysis of the recombinant BGLII revealed that transglycosylation products might be oligosaccharides, composed probably of glucose linked β-1,4, β-1,3, or a mixture of both. PC-3-7 revertants of bgl2 exhibited reduced expression and inducibility of cellulase during growth on cellulose and cellobiose substrates. Furthermore, the effect of this bgl2 mutation was reproduced in the common strain QM9414 in which the transformants showed cellulase production comparable to that of PC-3-7.Conclusion
We conclude that BGLII plays an important role in cellulase induction in T. reesei and that the bgl2 mutation in PC-3-7 brought about enhanced cellulase expression on cellobiose. The results of the investigation using PC-3-7 suggested that other mutation(s) in PC-3-7 could also contribute to cellulase induction. Further investigation is essential to unravel the mechanism responsible for cellulase induction in T. reesei.180.
Hidenaga Kobashi Kazutaka Kamiya Mohamed A. Ali Akihito Igarashi Mohamed Ehab M. Elewa Kimiya Shimizu 《PloS one》2015,10(4)