全文获取类型
收费全文 | 636篇 |
免费 | 51篇 |
国内免费 | 1篇 |
出版年
2022年 | 4篇 |
2021年 | 13篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 12篇 |
2017年 | 2篇 |
2016年 | 16篇 |
2015年 | 23篇 |
2014年 | 21篇 |
2013年 | 40篇 |
2012年 | 45篇 |
2011年 | 37篇 |
2010年 | 38篇 |
2009年 | 26篇 |
2008年 | 35篇 |
2007年 | 32篇 |
2006年 | 35篇 |
2005年 | 38篇 |
2004年 | 33篇 |
2003年 | 31篇 |
2002年 | 27篇 |
2001年 | 10篇 |
2000年 | 22篇 |
1999年 | 16篇 |
1998年 | 10篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 11篇 |
1992年 | 12篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1984年 | 9篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有688条查询结果,搜索用时 113 毫秒
81.
82.
Umeda C Sonoyama K Yamaguchi N Saito R Akashi K Motoshima H Kawabata J 《Bioscience, biotechnology, and biochemistry》2005,69(1):249-251
An increase in plasma ovalbumin concentrations after intragastric administration of ovalbumin was suppressed by concomitant freeze-dried kefir in BALB/c mice. Serum levels of ovalbumin-specific immunoglobulin G and proliferation of splenic mononuclear cells in mice immunized orally with ovalbumin were suppressed by feeding freeze-dried kefir. We propose that kefir reduces intestinal permeation of food antigen, which contributes to suppression of oral sensitization. 相似文献
83.
84.
Basic fibroblast growth factor (FGF-2) mitogenic activities of sulfonated poly(gamma-glutamic acid) (gamma-PGA-S) were investigated with chlorate-treated L929 fibroblast culture tests. When 72% of the carboxyl groups in gamma-PGA were sulfonated (gamma-PGA-S72), cell numbers reached a maximum. The activity of gamma-PGA-S72 was higher than that of gamma-PGA and synthetic heparinoids and was almost comparable to that of heparin. Cytotoxicity of gamma-PGA-S72 was not observed, regardless of the degree of sulfonation. FGF-2-protective effects of gamma-PGA-S72 against acid and thermal inactivation were also evaluated, and gamma-PGA-S72 showed higher FGF-2-protective effects in comparison to nonsulfonated gamma-PGA. The steric structures of various sulfonated gamma-PGA-Ss were analyzed by molecular modeling (molecular orbital method (MOPAC)) and indicated that gamma-PGA-Ss are helical in vacuo. Results from MOPAC and the molecular mechanics method (MM2) demonstrated that electrostatic interactions can take place between sulfonic and carboxyl groups of gamma-PGA-S and basic amino acid residues in FGF-2. gamma-PGA-S72 can interact with FGF-2 strongly. 相似文献
85.
Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta 总被引:1,自引:0,他引:1
Ohashi N Yamamoto T Uchida C Togawa A Fukasawa H Fujigaki Y Suzuki S Kitagawa K Hattori T Oda T Hayashi H Hishida A Kitagawa M 《FEBS letters》2005,579(12):2557-2563
Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7. We found that TGF-beta stimulates Smurf2 expression. TGF-beta activated the Smurf2 promoter in a TGF-beta responsive cell lines, whereas IL-1alpha, PDGF and epidermal growth factor did not. TGF-beta-mediated Smurf2 promoter activation was inhibited by Smad7 or an activin receptor-like kinase 5 inhibitor but not by dominant negative Smad or disruption of Smad-binding elements in the promoter. Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway suppressed TGF-beta-mediated Smurf2 induction. These results suggest that TGF-beta stimulates Smurf2 expression by Smad-independent pathway such as PI3K/Akt pathway via TGF-beta receptor. 相似文献
86.
Kondo H Park SH Watanabe K Yamamoto Y Akashi M 《Biochemical and biophysical research communications》2004,316(1):59-64
Green tea is a rich source of polyphenols, and (-)-epigallocatechin-3-gallate (EGCG) is a major constituent of green tea polyphenols. In the present study, we investigated the effect of EGCG on apoptosis induced by irradiation in the human keratinocytic cell line HaCaT. Irradiation by gamma-ray induced apoptosis with concomitant cleavage of caspase-3 and its in vivo substrate poly(ADP-ribose) polymerase. Treatment of cells with EGCG inhibited irradiation-induced apoptosis as detected by Hoechst staining and internucleosomal cleavage of DNA, and prevented the cleavage of these proteins by irradiation. We also found that the treatment of cells with EGCG alone suppressed cell growth and induced apoptosis in these cells. Our results suggest that EGCG inhibits irradiation-induced apoptosis by inactivating the caspase pathway in HaCaT cells. Our study also indicates that EGCG has a dual effect on the survival of these keratinocytes. 相似文献
87.
Cytochrome P450s in flavonoid metabolism 总被引:2,自引:0,他引:2
In this review, cytochrome P450s characterized at the molecular level catalyzing aromatic hydroxylations, aliphatic hydroxylations and skeleton formation in the flavonoid metabolism are surveyed. They are involved in the biosynthesis of anthocyanin pigments and condensed tannin (CYP75, flavonoid 3′,5′-hydroxylase and 3′-hydroxylase), flavones [CYP93B, (2S)-flavanone 2-hydroxylase and flavone synthase II], and leguminous isoflavonoid phytoalexins [CYP71D9, flavonoid 6-hydroxylase; CYP81E, isoflavone 2′-hydroxylase and 3′-hydroxylase; CYP93A, 3,9-dihydroxypterocarpan 6a-hydroxylase; CYP93C, 2-hydroxyisoflavanone synthase (IFS)]. Other P450s of the flavonoid metabolism include methylenedioxy bridge forming enzyme, cyclases producing glyceollins, flavonol 6-hydroxylase and 8-dimethylallylnaringenin 2′-hydroxylase. Mechanistic studies on the unusual aryl migration by CYP93C, regulation of IFS expression in plant organs and its biotechnological applications are introduced, and flavonoid metabolisms by non-plant P450s are also briefly discussed. 相似文献
88.
Belin RJ Sumandea MP Kobayashi T Walker LA Rundell VL Urboniene D Yuzhakova M Ruch SH Geenen DL Solaro RJ de Tombe PP 《American journal of physiology. Heart and circulatory physiology》2006,291(5):H2344-H2353
It is currently unclear whether left ventricular (LV) myofilament function is depressed in experimental LV hypertrophy (LVH) or congestive heart failure (CHF). To address this issue, we studied pressure overload-induced LV hypertrophy (POLVH) and myocardial infarction-elicited congestive heart failure (MICHF) in rats. LV myocytes were isolated from control, POLVH, and MICHF hearts by mechanical homogenization, skinned with Triton, and attached to micropipettes that projected from a sensitive force transducer and high-speed motor. A subset of cells was treated with either unphosphorylated, recombinant cardiac troponin (cTn) or cTn purified from either control or failing ventricles. LV myofilament function was characterized by the force-[Ca(2+)] relation yielding Ca(2+)-saturated maximal force (F(max)), myofilament Ca(2+) sensitivity (EC(50)), and cooperativity (Hill coefficient, n(H)) parameters. POLVH was associated with a 35% reduction in F(max) and 36% increase in EC(50). Similarly, MICHF resulted in a 42% reduction in F(max) and a 30% increase in EC(50). Incorporation of recombinant cTn or purified control cTn into failing cells restored myofilament Ca(2+) sensitivity toward levels observed in control cells. In contrast, integration of cTn purified from failing ventricles into control myocytes increased EC(50) to levels observed in failing myocytes. The F(max) parameter was not markedly affected by troponin exchange. cTnI phosphorylation was increased in both POLVH and MICHF left ventricles. We conclude that depressed myofilament Ca(2+) sensitivity in experimental LVH and CHF is due, in part, to a decreased functional role of cTn that likely involves augmented phosphorylation of cTnI. 相似文献
89.
Construction of an infectious clone of canine herpesvirus genome as a bacterial artificial chromosome 总被引:1,自引:0,他引:1
Arii J Hushur O Kato K Kawaguchi Y Tohya Y Akashi H 《Microbes and infection / Institut Pasteur》2006,8(4):1054-1063
Canine herpesvirus (CHV) is an attractive candidate not only for use as a recombinant vaccine to protect dogs from a variety of canine pathogens but also as a viral vector for gene therapy in domestic animals. However, developments in this area have been impeded by the complicated techniques used for eukaryotic homologous recombination. To overcome these problems, we used bacterial artificial chromosomes (BACs) to generate infectious BACs. Our findings may be summarized as follows: (i) the CHV genome (pCHV/BAC), in which a BAC flanked by loxP sites was inserted into the thymidine kinase gene, was maintained in Escherichia coli; (ii) transfection of pCHV/BAC into A-72 cells resulted in the production of infectious virus; (iii) the BAC vector sequence was almost perfectly excisable from the genome of the reconstituted virus CHV/BAC by co-infection with CHV/BAC and a recombinant adenovirus that expressed the Cre recombinase; and (iv) a recombinant virus in which the glycoprotein C gene was deleted was generated by lambda recombination followed by Flp recombination, which resulted in a reduction in viral titer compared with that of the wild-type virus. The infectious clone pCHV/BAC is useful for the modification of the CHV genome using bacterial genetics, and CHV/BAC should have multiple applications in the rapid generation of genetically engineered CHV recombinants and the development of CHV vectors for vaccination and gene therapy in domestic animals. 相似文献
90.
Essential role for cyclin D3 in granulocyte colony-stimulating factor-driven expansion of neutrophil granulocytes 下载免费PDF全文
Sicinska E Lee YM Gits J Shigematsu H Yu Q Rebel VI Geng Y Marshall CJ Akashi K Dorfman DM Touw IP Sicinski P 《Molecular and cellular biology》2006,26(21):8052-8060
The proliferation of neutrophil granulocyte lineage is driven largely by granulocyte colony-stimulating factor (G-CSF) acting via the G-CSF receptors. In this study, we show that mice lacking cyclin D3, a component of the core cell cycle machinery, are refractory to stimulation by the G-CSF. Consequently, cyclin D3-null mice display deficient maturation of granulocytes in the bone marrow and have reduced levels of neutrophil granulocytes in their peripheral blood. The mutant mice are unable to mount a normal response to bacterial challenge and succumb to microbial infections. In contrast, the expansion of hematopoietic stem cells and lineage-committed myeloid progenitors proceeds relatively normally in mice lacking cyclin D3, revealing that the requirement for cyclin D3 function operates at later stages of neutrophil development. Importantly, we verified that this requirement is specific to cyclin D3, as mice lacking other G(1) cyclins (D1, D2, E1, or E2) display normal granulocyte counts. Our analyses revealed that in the bone marrow cells of wild-type mice, activation of the G-CSF receptor leads to upregulation of cyclin D3. Collectively, these results demonstrate that cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they provide a molecular link of how G-CSF-dependent signaling triggers cell proliferation. 相似文献