全文获取类型
收费全文 | 2043篇 |
免费 | 22篇 |
国内免费 | 33篇 |
出版年
2024年 | 3篇 |
2023年 | 48篇 |
2022年 | 36篇 |
2021年 | 80篇 |
2020年 | 88篇 |
2019年 | 168篇 |
2018年 | 83篇 |
2017年 | 38篇 |
2016年 | 40篇 |
2015年 | 27篇 |
2014年 | 175篇 |
2013年 | 205篇 |
2012年 | 100篇 |
2011年 | 206篇 |
2010年 | 124篇 |
2009年 | 121篇 |
2008年 | 99篇 |
2007年 | 95篇 |
2006年 | 101篇 |
2005年 | 76篇 |
2004年 | 72篇 |
2003年 | 46篇 |
2002年 | 43篇 |
2001年 | 3篇 |
1998年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有2098条查询结果,搜索用时 265 毫秒
181.
Mouithys-Mickalad A Deby-Dupont G Mathy-Hartert M Habraken Y Nys M Henrotin Y Lamy M Deby C 《Biochemical and biophysical research communications》2004,318(4):941-948
We previously observed that the respiratory burst of human monocytes (THP-1 cell line) triggered by phorbol myristate acetate was strongly enhanced by a priming of the cells by Chlamydia pneumoniae [Biochem. Biophys. Res. Commun. 287 (2001) 781]. We describe here the modifications of the responses of Chlamydia-primed THP-1 cells to hydrocortisone (HCT) and methylprednisolone (MPL). HCT and MPL inhibited the production of the cytokines TNFα and IL-8. But HCT, which inhibited the respiratory burst in LPS-primed monocytes, paradoxically stimulated the phenomenon in Chlamydia-primed cells; MPL exerted no significant effect. Both glucocorticoids did not significantly modify the triggering effect of Chlamydia on NF-κB binding activity. On the expression of p22phox, a protein subunit of the NADPH oxidase, HCT had an increasing and MPL a decreasing effect. Glucocorticoids thus had unexpected effects on the inflammatory response of Chlamydia-primed monocytes. 相似文献
182.
Shibuya Y Hirasawa N Sakai T Togashi Y Muramatsu R Ishii K Yamashita M Takayanagi M Ohuchi K 《Life sciences》2004,75(4):435-446
The role of p44/42 mitogen-activated protein kinase (MAPK) in the expression of intercellular adhesion molecule-1 (ICAM-1) in NCI-H292 cells, a human bronchial epithelial cell line, was analyzed. Treatment with the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2 nM) or interferon-gamma (IFN-gamma) (100 U/ml) induced phosphorylation of p44/42 MAPK. The MEK inhibitor U0126 (0.1 to 10 microM) enhanced the TPA-induced ICAM-1 expression but not the IFN-gamma-induced one. U0126 also enhanced the ICAM-1 expression induced by two other PKC activators teleocidin (22.5 nM) and aplysiatoxin (14.9 nM). Furthermore, PD98059 (0.5 to 50 microM), another MEK inhibitor, enhanced the TPA-induced ICAM-1 expression as well. The inhibitor of p38 MAPK SB203580 did not affect the TPA-induced ICAM-1 expression. BAY11-7082, an inhibitor of nuclear factor kappaB (NF-kappaB) activation, and MG132, a 26S proteasome inhibitor, reduced the TPA-induced ICAM-1 expression but not the IFN-gamma-induced one. TPA partially decreased the level of IkappaB-alpha and the reduction was further augmented by U0126 in a concentration-dependent manner. These findings suggested that, in NCI-H292 cells, p44/42 MAPK suppresses PKC activator-induced NF-kappaB activation, thus negatively regulating the PKC activator-induced ICAM-1 expression but not the IFN-gamma-induced one. 相似文献
183.
184.
目的研究乳酸杆菌代谢物RNA组分对免疫细胞功能的影响,为进一步研究其可能存在的生物学功能打基础。方法采用细胞培养技术、Western Blot、ELISA和MTT等方法。结果乳酸杆菌代谢物RNA组分对全脾细胞和脾脏来源的DC增殖有促进作用,对骨髓来源的DC有抑制作用,它不刺激巨噬细胞数量增殖,但可以明显增强巨噬细胞的吞噬功能。用乳酸杆菌代谢物RNA组分冲激脾脏来源的DC可以轻微增强其杀伤YAC-1的作用和显著促进INF-γ分泌,但相同条件下对BMDC杀伤YAC-1的作用是抑制的,能抑制BMDC分泌INF-γ,但可以增加BMDC刺激全脾细胞的增殖和NF-κB的表达上调。结论乳酸杆菌代谢物RNA组分对小鼠免疫细胞功能具有调节作用。 相似文献
185.
Laiqun Zhang 《Journal of molecular biology》2010,396(3):528-539
Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and receptor-interacting protein 1 (RIP1) play critical roles in activating c-Jun N-terminal kinase (JNK) and inhibitor of κB kinase (IKK), as well as in inhibiting apoptosis induced by TNFα. The TRAF2 RING domain-mediated polyubiquitination of RIP1 is believed to be essential for TNFα-induced IKK activation, and the RING-domain-deleted TRAF2 (TRAF2-ΔR) has been widely used as a dominant negative in transient overexpression systems to block TNFα-induced JNK and IKK activation. Here, we report that stable expression of TRAF2-ΔR at a physiological level in TRAF2 and TRAF5 double knockout (TRAF2/5 DKO) cells almost completely restores normal TNFα-induced IKK activation, but not RIP1 polyubiquitination. In addition, stable expression of TRAF2-ΔR in TRAF2/5 DKO cells efficiently inhibited the TNFα-induced later phase of prolonged JNK activation, yet failed to inhibit TNFα-induced cell death. Although the basal and inducible expression of anti-apoptotic proteins in TRAF2-ΔR-expressing TRAF2/5 DKO cells was normal, the cells remained sensitive to TNFα-induced cell death because anti-apoptotic proteins were not recruited to the TNFR1 complex efficiently. Moreover, stable expression of TRAF2-ΔR in TRAF2/5 DKO cells failed to suppress constitutive p100 processing in these cells. These data suggest that (i) the TRAF2 RING domain plays a critical role in inhibiting cell death induced by TNFα and is essential for suppressing the noncanonical nuclear factor κB pathway in unstimulated cells; (ii) RIP1 polyubiquitination is not essential for TNFα-induced IKK activation; and (iii) prolonged JNK activation has no obligate role in TNFα-induced cell death. 相似文献
186.
187.
Trzemecka A Jacewicz A Carver GT Drake JW Bebenek A 《Journal of molecular biology》2010,404(5):778-793
Phage RB69 B-family DNA polymerase is responsible for the overall high fidelity of RB69 DNA synthesis. Fidelity is compromised when conserved Tyr567, one of the residues that form the nascent polymerase base-pair binding pocket, is replaced by alanine. The Y567A mutator mutant has an enlarged binding pocket and can incorporate and extend mispairs efficiently. Ser565 is a nearby conserved residue that also contributes to the binding pocket, but a S565G replacement has only a small impact on DNA replication fidelity. When Y567A and S565G replacements were combined, mutator activity was strongly decreased compared to that with Y567A replacement alone. Analyses conducted both in vivo and in vitro revealed that, compared to Y567A replacement alone, the double mutant mainly reduced base substitution mutations and, to a lesser extent, frameshift mutations. The decrease in mutation rates was not due to increased exonuclease activity. Based on measurements of DNA binding affinity, mismatch insertion, and mismatch extension, we propose that the recovered fidelity of the double mutant may result, in part, from an increased dissociation of the enzyme from DNA, followed by the binding of the same or another polymerase molecule in either exonuclease mode or polymerase mode. An additional antimutagenic factor may be a structural alteration in the polymerase binding pocket described in this article. 相似文献
188.
189.
190.
The acid polysaccharide fraction (APSF) extracted from the mycelia of cultivated Cordyceps sinensis is water-soluble polysaccharide. In this study we evaluated the modulating effects of APSF on murine macrophage cell line RAW264.7. Phagocytotic assay by neutral red and FITC-dextran internalization showed that APSF stimulated the phagocytosis of macrophages. The nitrite levels in the culture supernatant determined using Griess reagent revealed the elevation of NO production after treatment with APSF. RT-PCR and immunocytochemistry assay indicated that APSF promoted both the mRNA and protein expressions of inducible nitric oxide synthase (iNOS). Furthermore, Western blotting demonstrated that NF-κB levels in nucleuses increased after APSF treatment, suggesting that APSF probably stimulated macrophage activities by activating the IκB-NF-κB pathway. 相似文献