全文获取类型
收费全文 | 298篇 |
免费 | 22篇 |
出版年
2022年 | 3篇 |
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 6篇 |
2016年 | 4篇 |
2015年 | 8篇 |
2014年 | 19篇 |
2013年 | 19篇 |
2012年 | 28篇 |
2011年 | 28篇 |
2010年 | 10篇 |
2009年 | 23篇 |
2008年 | 29篇 |
2007年 | 11篇 |
2006年 | 7篇 |
2005年 | 18篇 |
2004年 | 10篇 |
2003年 | 13篇 |
2002年 | 15篇 |
2001年 | 7篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
排序方式: 共有320条查询结果,搜索用时 593 毫秒
31.
Seema Jagota Jayakumar Rajadas 《International journal of peptide research and therapeutics》2012,18(1):53-61
Genetic, biochemical and pathological evidence support that self-assembly of amyloid-beta (Aβ) peptide into toxic aggregates
is implicated as the cause of Alzheimer’s disease. An attractive therapeutic strategy for the treatment of AD is to prevent
or interfere with Aβ aggregation. A systematic investigation of the effects of proline-, glycine-, arginine- and lysine- containing
peptides (PGKLVYA, KKLVFFARRRRA and KKLVFFA) on the beta-amyloid aggregation was made using FTIR, circular dichroism, ANS
binding, ThT binding and TEM analysis. These peptides are based on the central hydrophobic region of Aβ (residues 16–20),
which is believed to be crucial in Aβ self-association. There is increasing evidence to suggest that protein aggregation,
including amyloid fibril formation results from the strong self-association tendency of the partially folded intermediates.
Addition of PGKLVYA and KKLVFFARRRRA resulted in increase in ANS fluorescence intensity, suggesting enhanced exposure of hydrophobic
surface area. As observed by ThT and TEM analysis PGKLVYA and KKLVFFARRRRA promote non-fibrillar ensembles, while peptide
KKLVFFA accelerated the fibrillization of Aβ peptide by stabilizing intermolecular interactions. Circular dichroism and FTIR
data showed that PGKLVYA and KKLVFFARRRRA effectively prevented amyloid-beta (Aβ) peptide adopting the beta-sheet secondary
structure correlated with fibrillogenesis. This result indicates that PGKLVYA and KKLVFFARRRRA might have triggered another
mechanism of Aβ assembly. 相似文献
32.
33.
34.
Tao Yang Juliet K. Knowles Qun Lu Hong Zhang Ottavio Arancio Laura A. Moore Timothy Chang Qian Wang Katrin Andreasson Jayakumar Rajadas Gerald G. Fuller Youmei Xie Stephen M. Massa Frank M. Longo 《PloS one》2008,3(11)
The p75 neurotrophin receptor (p75NTR) is expressed by neurons particularly vulnerable in Alzheimer''s disease (AD). We tested the hypothesis that non-peptide, small molecule p75NTR ligands found to promote survival signaling might prevent Aβ-induced degeneration and synaptic dysfunction. These ligands inhibited Aβ-induced neuritic dystrophy, death of cultured neurons and Aβ-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Aβ-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3β and c-Jun, and tau phosphorylation, and prevented Aβ-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked Aβ-induced hippocampal LTP impairment. These studies support an extensive intersection between p75NTR signaling and Aβ pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Aβ-induced neuronal dystrophy and death. 相似文献
35.
Jesudason EP Masilamoni JG Ashok BS Baben B Arul V Jesudoss KS Jebaraj WC Dhandayuthapani S Vignesh S Jayakumar R 《Molecular and cellular biochemistry》2008,311(1-2):145-156
Aβ amyloid peptide is believed to induce oxidative stress leading to inflammation, which is postulated to play a significant
role in the toxicity of Alzheimer’s disease (AD). This study was designed to investigate the inhibitory effects of dl-α lipoic acid (LA), a potential free radical scavenger, on oxidative vulnerability induced by intraperitoneal injection of
Aβ25–35 amyloid fibrils in mice. Mice were divided into three groups: control, Aβ amyloid toxicity induced (AT), and LA treated (ATL).
Blood Plasma was separated, liver, spleen and brain were dissected and analysis of oxidants, antioxidants, ATPases, glial
fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NFκB) were carried out. Results show biochemical parameters such
as reactive oxygen species (ROS) and lipid peroxidation (LPO) were significantly lowered (P < 0.05) and levels of antioxidants and ATPase (P < 0.05) were significantly increased (P < 0.05) in hepatocytes, splenocytes and astrocytes of the ATL group. Moreover, our histological results revealed a decreased
GFAP immunoreactivity in the neocortical region and NFκB immunoreactivity in neocortex, liver and spleen. This study reiterates
LA as a potent free radical scavenger to combat oxidative vulnerability in the treatment for Aβ amyloid toxicity. 相似文献
36.
Sambasivam D Liu CW Jayaraman M Malar EJ Rajadas J 《Biochimica et biophysica acta》2008,1784(11):1659-1667
Most of the disease causing proteins such as beta amyloid, amylin, and huntingtin protein, which are natively disordered, readily form fibrils consisting of beta-sheet polymers. Though all amyloid fibrils are made up of beta-sheet polymers, not all peptides with predominant beta-sheet content in the native state develop into amyloid fibrils. We hypothesize that stable amyloid like fibril formation may require mixture of different conformational states in the peptide. We have tested this hypothesis on amyloid forming peptide namely HCl(Ile)(5)NH(CH(2)CH(2)O)(3)CH(3) (I). We show peptide I, has propensity to form self-assembled structures of beta-sheets in aqueous solutions. When incubated over a period of time in aqueous buffer, I self assembled into beta sheet like structures with diameters ranging from 30 to 60 A that bind with amyloidophilic dyes like Congo red and Thioflavin T. Interestingly peptide I developed into unstable fibrils after prolonged aging at higher concentration in contrast with the general mature fibril-forming propensity of various amyloid petides known to date. 相似文献
37.
38.
S. Raj V. Vinod J. Jayakumar P. Suresh A. Kumar R. Biswas 《Letters in applied microbiology》2021,73(1):31-38
Candida species are opportunistic human fungal pathogens that cause acute and chronic infections against which only few antifungal agents are available. Here we have elucidated the antifungal effect of Syzygium samarangense leaf extracts (SSLE). Antifungal activity of SSLE was studied against Candida albicans, C. krusei, C. parapsilosis, C. glabrata, C. auris and C. tropicalis. Following experiments were performed: minimum fungicidal concentration (MFC) determination, agar well disc diffusion assays, fungal morphology analysis using scanning electron microscope (SEM), ex vivo fungal survival assays on porcine tongue and skin and in vivo fungal survival assays using Drosophila melanogaster fly model. Results demonstrated MFC of SSLE ranges between 100 and 125 mg ml−1. SEM images showed cell wall degradation of C. albicans when treated with SSLE. Around 75% decrease in C. albicans viability was observed when infected porcine tongue and skin were treated using SSLE. The C. albicans infected D. melanogaster when fed with SSLE showed significant decrease (around 80%) of fungal count than the infected control. Furthermore, agar plate disc diffusion assays demonstrated that the antifungal activity of SSLE could be due to chalcone, which is one of the active constituents in SSLE. Our study demonstrated that SSLE could be used for the topical treatment of Candida infections. 相似文献
39.
Sivakumar Allur Subramaniyan Sunirmal Sheet Saravanakumar Balasubramaniam Swami Vetha Berwin Singh Dileep Reddy Rampa Sureshkumar Shanmugam 《Cell communication & adhesion》2018,24(1):19-32
The objective of this study was to synthesize and characterize novel polyurethane (PU)-nanofiber coated with l-arginine by electrospinning technique. This study determined whether l-arginine conjugated with PU-nanofiber could stimulate cell proliferation and prevent H2O2-induced cell death in satellite cells co-cultured with fibroblasts isolated from Hanwoo (Korean native cattle). Our results showed that l-arginine conjugated with PU nanofiber could reduce cytotoxicity of co-cultured satellite cells. Protein expression levels of bcl-2 were significantly upregulated whereas those of caspase-3 and caspase-7 were significantly downregulated in co-culture of satellite cells compared to those of monoculture cells after treatment with PU-nanofiber coated with l-arginine and which confirmed by Confocal microscope. These results suggest that co-culture of satellite cells with fibroblasts might be able to counter oxidative stress through translocation/penetration of antioxidant, collagen, and molecules secreted to satellite cells. Therefore, this nanofiber might be useful as a wound dressing in animals to counter oxidative stresses. 相似文献
40.
Shah Ahmed Belal Allur Subramaniyan Sivakumar Da Rae Kang Sangbuem Cho Ho Sung Choe 《Animal cells and systems.》2018,22(5):324-333
This study was performed to elucidate the effects of linoleic acid (LA), oleic acid (OA) and their combination (LA?+?OA) on cell proliferation, apoptosis, necrosis, and the lipid metabolism related gene expression in bovine satellite cells (BSCs), isolated from bovine muscles. Cell viability was significantly increased with the OA and LA treatment. Furthermore, LA?+?OA enhanced cell proliferation in a dose-dependent manner (10 to 100?µM), whereas it lowered at 250?µM. In addition, a cell-cycle analysis showed that 100?µM of LA and OA markedly decreased the G0/G1 phase proportion (62.58% and 61.33%, respectively), compared to controls (68.02%), whereas the S-phase cells’ proportion was increased. The ratio of G2/M phase cells was not significantly different among the groups. Moreover, analyses with AO/EtBr staining showed that no apoptosis occurred. Necrosis were determined by flow cytometry using Annexin V-FITC/PI staining which revealed no early apoptosis in the cells pretreated with LA or OA, but occurred in the LA?+?OA group. We also analyzed the mRNA expression of lipid metabolizing genes such as peroxisome proliferator receptor alfa (PPARα), peroxisome proliferator receptor gamma (PPARγ), acyl-CoA oxidase (ACOX), lipoprotein lipase (LPL), carnitine palmitoyl transferase (CPT-1), and fatty-acid binding protein4 (FABP4), which were upregulated in LA or OA treated cells compared to the control group. In essence, LA and OA alone promote the cell proliferation without any apoptosis and necrosis, which might upregulate the lipid metabolism related gene expressions, and increase fatty-acid oxidation in the BSCs’ lipid metabolism. 相似文献