全文获取类型
收费全文 | 413篇 |
免费 | 20篇 |
国内免费 | 2篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 9篇 |
2019年 | 15篇 |
2018年 | 10篇 |
2017年 | 6篇 |
2016年 | 19篇 |
2015年 | 10篇 |
2014年 | 27篇 |
2013年 | 40篇 |
2012年 | 35篇 |
2011年 | 35篇 |
2010年 | 18篇 |
2009年 | 14篇 |
2008年 | 21篇 |
2007年 | 19篇 |
2006年 | 13篇 |
2005年 | 8篇 |
2004年 | 13篇 |
2003年 | 18篇 |
2002年 | 7篇 |
2001年 | 12篇 |
2000年 | 11篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 5篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 5篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有435条查询结果,搜索用时 62 毫秒
61.
Peramaiyan Rajendran Thamaraiselvan Rengarajan Yutaka Nishigaki Rajendran Palaniswami Ikuo Nishigaki 《Journal of receptor and signal transduction research》2016,36(1):57-66
The therapeutic effects of the natural antioxidant mangiferin (a xanthonoid and potent oxygen free radical scavenger), which is widely distributed in mango fruit, against CdCl2-induced toxicity in human renal glomerulus endothelial cells (HRGEC) were investigated. The viability of HREGCs that were treated with CdCl2 (25?µ?mol) and co-treated with mangiferin (75?µ?mol) for 24?h was measured by crystal violet dye. The exposure of human glomerulus renal endothelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal proinflammatory cytokines known to play a significant role in renal inflammation. Proinflammatory cytokine secretion by human renal glomerulus endothelial cells could be the result of cadmium-induced IL-6 secretion via an NF-κB-dependent pathway. However, IL-8 secretion involves the phosphor-JNK phospho-p38 signaling pathway. The results of the current study reveal that mangiferin could prevent both cadmium-induced IL-6 and IL-8 secretion by human glomerulus endothelial cells and be used to prevent renal inflammation. 相似文献
62.
63.
64.
Burki Rajendar Arivazhagan Rajendran Yusuke Sato Seiichi Nishizawa Norio Teramae 《Bioorganic & medicinal chemistry》2009,17(1):351-359
Isoxanthopterin (IX) has two edges with hydrogen bond-forming sites suitable for binding to thymine (T) and cytosine (C). The binding affinity of IX for T or C is stronger than for adenine (A) and guanine (G), whereas the base selectivity of IX for T over C (and vice versa) is moderate. In order to improve both the binding affinity and base selectivity for T over C or C over T, a methyl group is introduced respectively at the N-3 or N-8 position of IX. This leads to the known ligands 3-methyl isoxanthopterin (3-MIX) and 8-methyl isoxanthopterin (8-MIX), and the binding affinity for C or T is expected to be tuned and improved by methyl substitution. Indeed, 3-MIX selectively binds to T more strongly than IX with a binding constant of 1.5 × 106 M?1 and it loses its binding affinity for C. In contrast, 8-MIX selectively binds to C over T with a binding constant of 1.0 × 106 M?1 and the binding affinity is greatly improved compared to the parent ligand IX. The thermodynamics of the ligand–nucleotide interaction is analyzed by isothermal calorimetric titrations, and the results show that the interaction follows a 1:1 stoichiometry and is enthalpy-driven. The introduction of methyl groups at both N-3 and N-8 positions results in an increase in enthalpy of the ligand–nucleotide interaction, which leads to the improved binding affinity. 相似文献
65.
Rajeevkumar Raveendran Sudarsana Devi Suma Priya Madhavan Mayadevi Mathew Steephan Thankayyan R. Santhoshkumar John Cheriyan Rajendran Sanalkumar Kurup K. Pradeep Jackson James Ramakrishnapillai V. Omkumar 《Journal of neurochemistry》2009,110(1):92-105
Ca2+ influx through NMDA-type glutamate receptor at excitatory synapses causes activation of post-synaptic Ca2+ /calmodulin-dependent protein kinase type II (CaMKII) and its translocation to the NR2B subunit of NMDA receptor. The major binding site for CaMKII on NR2B undergoes phosphorylation at Ser1303, in vivo . Even though some regulatory effects of this phosphorylation are known, the mode of dephosphorylation of NR2B-Ser1303 is still unclear. We show that phosphorylation status at Ser1303 enables NR2B to distinguish between the Ca2+ /calmodulin activated form and the autonomously active Thr286-autophosphorylated form of CaMKII. Green fluorescent protein–α-CaMKII co-expressed with NR2B sequence in human embryonic kidney 293 cells was used to study intracellular binding between the two proteins. Binding in vitro was studied by glutathione- S -transferase pull-down assay. Thr286-autophosphorylated α-CaMKII or the autophosphorylation mimicking mutant, T286D-α-CaMKII, binds NR2B sequence independent of Ca2+ /calmodulin unlike native wild-type α-CaMKII. We show enhancement of this binding by Ca2+ /calmodulin. Phosphorylation or a phosphorylation mimicking mutation on NR2B (NR2B-S1303D) abolishes the Ca2+ /calmodulin-independent binding whereas it allows the Ca2+ /calmodulin-dependent binding of α-CaMKII in vitro . Similarly, the autonomously active mutants, T286D-α-CaMKII and F293E/N294D-α-CaMKII, exhibited Ca2+ -independent binding to non-phosphorylatable mutant of NR2B under intracellular conditions. We also show for the first time that phosphatases in the brain such as protein phosphatase 1 and protein phosphatase 2A dephosphorylate phospho-Ser1303 on NR2B. 相似文献
66.
67.
Simon Rajendran Slawomir Salwa Xuefeng Gao Sabin Tabirca Deirdre O'Hanlon Gerald C. O'Sullivan Mark Tangney 《Journal of visualized experiments : JoVE》2010,(41)
This video describes the establishment of liver metastases in a mouse model that can be subsequently analysed by bioluminescent imaging. Tumour cells are administered specifically to the liver to induce a localised liver tumour, via mobilisation of the spleen and splitting into two, leaving intact the vascular pedicle for each half of the spleen. Lewis lung carcinoma cells that constitutively express the firefly luciferase gene (luc1) are inoculated into one hemi-spleen which is then resected 10 minutes later. The other hemi-spleen is left intact and returned to the abdomen. Liver tumour growth can be monitored by bioluminescence imaging using the IVIS whole body imaging system. Quantitative imaging of tumour growth using IVIS provides precise quantitation of viable tumour cells. Tumour cell death and necrosis due to drug treatment is indicated early by a reduction in the bioluminescent signal. This mouse model allows for investigating the mechanisms underlying metastatic tumour-cell survival and growth and can be used for the evaluation of therapeutics of liver metastasis. Download video file.(57M, mp4) 相似文献
68.
Cells without intact mitochondrial DNA have been shown to lack the bystander effect, which is an energy-dependent process. We hypothesized that cells harboring mutations in mitochondrial genes responsible for ATP synthesis would show a decreased bystander effect compared to normal cells. Radiation-induced bystander effects were analyzed in two normal and four mitochondrial mutant human lymphoblastoid cells. Medium from previously irradiated cells (conditioned medium) was transferred to unirradiated cells from the respective cell lines and evaluated for the bystander effect using the cytokinesis-block micronucleus assay. Unlike normal cells that were used as a control, mitochondrial mutant cells neither generated nor responded to the bystander signals. The bystander effect was inhibited in normal cells by adding the mitochondrial inhibitors rotenone and oligomycin to the culture medium. Time-controlled blocking of the bystander effect by inhibitors was found to occur either for prolonged exposure to the inhibitor prior to irradiation with an immediate and subsequent removal of the inhibitors or immediate post-application of the inhibitor. Adding the inhibitors just prior to irradiation and removing them immediately after irradiation was uneventful. Fully functional mitochondrial metabolic capability may therefore be essential for the bystander effect. 相似文献
69.
Ramage G Rajendran R Gutierrez-Correa M Jones B Williams C 《FEMS microbiology letters》2011,324(2):89-97
The biofilm phenotype is an increasingly important concept in mycological research. Recently, there has been a developing interest in whether Aspergillus species are truly able to form biofilms or not. Industrial mycologists have long been aware of biofilms and their benefit in fermentation processes, whereas clinically their role is uncertain. This review provides an update on the impact that Aspergillus biofilms have medically and industrially, and will discuss biofilm development, and our current understanding of its molecular basis. The role of exopolymeric substance and how this substance relates to antimicrobial recalcitrance will also be discussed. 相似文献
70.
Rajendran V Saxena A Doctor BP Kozikowski AP 《Bioorganic & medicinal chemistry letters》2002,12(11):1521-1523
The synthesis and acetylcholinesterase inhibition activity of analogues of huperzine B are reported. These new racemic analogues show a better AChE inhibitory activity than the natural product huperzine B. 相似文献