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51.
52.
Heirman I Ginneberge D Brigelius-Flohé R Hendrickx N Agostinis P Brouckaert P Rottiers P Grooten J 《Free radical biology & medicine》2006,40(2):285-294
Using tumor cell-restricted overexpression of glutathione peroxidase 4 (GP x 4), we investigated the contribution of tumor cell eicosanoids to solid tumor growth and malignant progression in two tumor models differing in tumorigenic potential. By lowering cellular lipid hydroperoxide levels, GP x 4 inhibits cyclooxygenase (COX) and lipoxygenase (LOX) activities. GP x 4 overexpression drastically impeded solid tumor growth of weakly tumorigenic L929 fibrosarcoma cells, whereas B16BL6 melanoma solid tumor growth was unaffected. Yet, GP x 4 overexpression did markedly increase the sensitivity of B16BL6 tumors to angio-destructive TNF-alpha therapy and abolished the metastatic lung colonizing capacity of B16BL6 cells. Furthermore, the GP x 4-mediated suppression of tumor cell prostaglandin E(2) (PGE(2)) production impeded the induction of COX-2 expression by the tumor stress conditions hypoxia and inflammation. Thus, our results reflect a PGE(2)-driven positive feedback loop for COX-2 expression in tumor cells. This was further supported by the restoration of COX-2 induction capacity of GP x 4-overexpressing L929 tumor cells when cultured in the presence of exogenous PGE(2). Thus, although COX-2 expression and eicosanoid production may be enabled by PGE(2) from the tumor microenvironment, our results demonstrate the predominant tumor cell origin of protumoral eicosanoids, promoting solid tumor growth of weakly tumorigenic tumors and malignant progression of strongly tumorigenic tumors. 相似文献
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A stably transfected CHO cell line (LUCLEAD) was used where the coding region of native Firefly luciferase was linked to the 3'-UTR of the bovine growth hormone, and the 5'-nucleotides coding for the albumin signal peptide were linked to the N-terminal end of the luciferase coding region. Incubation of cells with 1 or 2 mM sodium butyrate (SB) for 72 h had no effect on cell growth since cultures reached confluency at the same time as control cells. Although cell cultures incubated with SB at a concentration of 4 mM were only about 60% confluent the luciferase content was about 5-fold higher than that in control cells. Cells incubated with either 1 or 2 mM SB showed intermediate levels of luciferase content. The amount of the chaperone BiP in the cells was not affected by incubation with SB. The results indicate that SB can be used to effectively promote synthesis of recombinant luciferase. 相似文献
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56.
Nawrotzki R Islinger M Vogel I Völkl A Kirsch J 《Histochemistry and cell biology》2012,137(4):471-482
Gephyrin is a scaffolding protein required for the accumulation of inhibitory neurotransmitter receptors at neuronal postsynaptic
membranes. In non-neuronal tissues, gephyrin is indispensible for the biosynthesis of molybdenum cofactor, the prosthetic
group of oxidoreductases including sulfite oxidase and xanthine oxidase. However, the molecular and cellular basis of gephyrin’s
non-neuronal function is poorly understood; in particular, the roles of its splice variants remain enigmatic. Here, we used
cDNA screening as well as Northern and immunoblot analyses to show that mammalian liver contains only a limited number of
gephyrin splice variants, with the C3-containing variant being the predominant isoform. Using new and established anti-gephyrin
antibodies in immunofluorescence and subcellular fractionation studies, we report that gephyrin localizes to the cytoplasm
of both tissue hepatocytes and cultured immortalized cells. These findings were corroborated by RNA interference studies in
which the cytosolic distribution was found to be abolished. Finally, by blue-native PAGE we show that cytoplasmic gephyrin
is part of a ~600 kDa protein complex of yet unknown composition. Our data suggest that the expression pattern of non-neuronal
gephyrin is simpler than indicated by previous evidence. In addition, gephyrin’s presence in a cytosolic 600 kDa protein complex
suggests that its metabolic and/or other non-neuronal functions are exerted in the cytoplasm and are not confined to a particular
subcellular compartment. 相似文献
57.
Background
There is dilemma as to whether patients infected with the Human Immunodeficiency Virus (HIV) requiring implant orthopaedic surgery are at an increased risk for post-operative surgical site infection (SSI). We conducted a systematic review to determine the effect of HIV on the risk of post-operative SSI and sought to determine if this risk is altered by antibiotic use beyond 24 hours.Methods
We searched electronic databases, manually searched citations from relevant articles, and reviewed conference proceedings. The risk of postoperative SSI was pooled using Mantel-Haenszel method.Results
We identified 18 cohort studies with 16 mainly small studies, addressing the subject. The pooled risk ratio of infection in the HIV patients when compared to non-HIV patients was 1.8 (95% Confidence Interval [CI] 1.3–2.4), in studies in Africa this was 2.3 (95% CI 1.5–3.5). In a sensitivity analysis the risk ratio was reduced to 1.4 (95% CI 0.5–3.8). The risk ratio of infection in patients receiving prolonged antibiotics compared to patients receiving antibiotics for up to 24 hours was 0.7 (95% CI 0.1–4.2).Conclusions
The results may indicate an increased risk in HIV infected patients but these results are not robust and inconclusive after conducting the sensitivity analysis removing poor quality studies. There is need for larger good quality studies to provide conclusive evidence. To better develop surgical protocols, further studies should determine the effect of reduced CD4 counts, viral load suppression and prolonged antibiotics on the risk for infection. 相似文献58.
Ingeborg M.M. van Leeuwen Bhavya Rao Marijke C.C. Sachweh Sonia Laín 《Cell cycle (Georgetown, Tex.)》2012,11(9):1851-1861
Pharmacological activation of wild-type p53 has been found to protect normal cells in culture from cytotoxicity and nuclear aberrations caused by conventional cancer therapeutics. Hence, small-molecule p53 activators could have clinical benefits as chemoprotectants for cancer patients bearing p53-mutant tumors. We have evaluated 16 p53-based cyclotherapy regimes combining p53 activators tenovin-6, leptomycin B, nutlin-3 and low dose actinomycin D, with clinically utilized chemotherapeutic agents (S- and M-phase poisons), vinblastine, vinorelbine, cytosine arabinoside and gemcitabine. All the p53 activators induce reversible cell-cycle arrest in primary human fibroblasts and protect them from both S- and M-phase poisons. Furthermore, studies with p53-mutant cancer cell lines show that nutlin-3 and low dose actinomycin D do not affect the sensitivity of these cells to any of the chemotherapeutics tested. Thus, these two small molecules could be suitable choices for cyclotherapy regimes involving S- or M-phase poisons. In contrast, pre-incubation of p53-mutant cells with tenovin-6 or leptomycin B reduces the efficacy of vinca alkaloids, suggesting that these p53 activators could be effective as chemoprotectants if combined with S- but not M-phase poisons. Discrepancies were observed between the levels of protection detected immediately after treatment and following recovery in fresh medium. This highlights the need to assess both short- and long-term effects when evaluating compounds as potential chemoprotectants for cancer therapy. 相似文献
59.
Garne E Loane M Dolk H Barisic I Addor MC Arriola L Bakker M Calzolari E Matias Dias C Doray B Gatt M Melve KK Nelen V O'Mahony M Pierini A Randrianaivo-Ranjatoelina H Rankin J Rissmann A Tucker D Verellun-Dumoulin C Wiesel A 《Birth defects research. Part A, Clinical and molecular teratology》2012,94(3):134-140
60.
Three unsprayed coffee farms (farm 1, 2 and 3) were studied for the natural occurrence of the insect pathogenic fungus Beauveria bassiana in Hypothenemus hampei populations throughout the rainy season of 2004 (July-November) and 2005 (July-December). B. bassiana infections were found during most sampling dates in both years, on all three farms. The B. bassiana infection levels were higher in 2005 than in 2004 with mean prevalence of 12.1% and 2.7%, respectively. No consistent significant differences in infection level between farms were found in any of the years. B. bassiana infection levels fluctuated widely throughout the season, and peaked at 13.5% on farm 3 in 2004 and at 44.0% on farm 1 in 2005. The H. hampei population was significantly higher in 2004 than in 2005, with 6.9% of the berries infested in 2004 and only 0.7% in 2005. In both years, the H. hampei infestation level was significantly higher on farm 2. No consistent significant differences in H. hampei infestation levels were found between sampling dates on any of the farms. H. hampei infestation levels fluctuated throughout both seasons, and peaked at 15.3% on farm 2 in 2004 and 2.2% on farm 2 in 2005. No consistent density dependent correlation between H. hampei infestation level and B. bassiana infection level was found. Correlations between climatic conditions and B. bassiana or H. hampei were not found. 相似文献