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11.
Swati Agarwal Shashi Kant Tiwari Brashket Seth Anuradha Yadav Anshuman Singh Anubha Mudawal Lalit Kumar Singh Chauhan Shailendra Kumar Gupta Vinay Choubey Anurag Tripathi Amit Kumar Ratan Singh Ray Shubha Shukla Devendra Parmar Rajnish Kumar Chaturvedi 《The Journal of biological chemistry》2015,290(34):21163-21184
The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA-induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down-regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell''s compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure. 相似文献
12.
A soluble β-galactoside binding 14.5 kDa lectin was purified from the heart of Capra hircus. Its metal independent nature, preferential affinity for β-d-lactose and 90–94% homology with carbohydrate recognition domain of previously reported galectin-1 confirmed its inclusion
in galectin-1 subfamily. The secondary structures of the deduced amino acid sequences were generally conserved with previously
reported Gal-1. Exposure of the purified protein to varying temperature and pH, oxidant, thiol blocking reagents, denaturants
and detergents resulted in significant changes in UV (ultraviolet), fluorescence, CD (circular dichroism) and FTIR (fourier
transform infra red) spectra, thus strongly emphasizing the vitality of regular secondary structure of galectins for maintaining
their active conformation. Bioinformatics studies corroborated the results obtained in wet lab. Our findings based on physico-chemical
properties, oxidative inactivation and structural analysis of the goat heart galectin-1 suggests significant implications
in potential biological and clinical applications. 相似文献
13.
Flinn B Rothwell C Griffiths R Lägue M DeKoeyer D Sardana R Audy P Goyer C Li XQ Wang-Pruski G Regan S 《Plant molecular biology》2005,59(3):407-433
To help develop an understanding of the genes that govern the developmental characteristics of the potato (Solanum tuberosum), as well as the genes associated with responses to specified pathogens and storage conditions, The Canadian Potato Genome
Project (CPGP) carried out 5′ end sequencing of regular, normalized and full-length cDNA libraries of the Shepody potato cultivar,
generating over 66,600 expressed sequence tags (ESTs). Libraries sequenced represented tuber developmental stages, pathogen-challenged
tubers, as well as leaf, floral developmental stages, suspension cultured cells and roots. All libraries analysed to date
have contributed unique sequences, with the normalized libraries high on the list. In addition, a low molecular weight library
has enhanced the 3′ ends of our sequence assemblies. Using the combined assembly dataset, unique tuber developmental, cold
storage and pathogen-challenged sequences have been identified. A comparison of the ESTs specific to the pathogen-challenged
tuber and foliar libraries revealed minimal overlap between these libraries. Mixed assemblies using over 189,000 potato EST
sequences from CPGP and The Institute for Genomics Research (TIGR) has revealed common sequences, as well as CPGP- and TIGR-unique
sequences.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users. 相似文献
14.
15.
Hua-Poo Su Youwei Yan G. Sridhar Prasad Robert F. Smith Christopher L. Daniels Pravien D. Abeywickrema John C. Reid H. Marie Loughran Maria Kornienko Sujata Sharma Jay A. Grobler Bei Xu Vinod Sardana Timothy J. Allison Peter D. Williams Paul L. Darke Daria J. Hazuda Sanjeev Munshi 《Journal of virology》2010,84(15):7625-7633
16.
Dave RS 《FEMS immunology and medical microbiology》2012,64(2):228-236
Opiate-abusing individuals are in the top three risk-factor groups for HIV infection. In fact, almost 30% of HIV-infected individuals in the USA are reported to abuse opiates, highlighting the intersection of drugs of abuse with HIV/AIDS. Opiate-abusers are cognitively impaired and suffer from neurological dysfunctions that may lead to high-risk sexual behavior, poor adherence to antiretroviral regimens, and hepatitis-C virus infection. Collectively, these factors may contribute to accelerated HIV central nervous system (CNS) disease progression. To understand the role of morphine in disease progression, we sought to determine whether morphine influences HIV-induced inflammation or viral replication in human monocyte-derived macrophages (h-mdms) and MAGI cells infected with HIV and exposed to morphine. Chronic morphine exposure of HIV-infected h-mdms led to significant alterations in the secretion of IL-6 and monocyte chemoattractant protein 2 (MCP-2). Morphine enhanced IL-6 secretion and blunted MCP-2 secretion from HIV-infected h-mdms. However, exposure of HIV-infected h-mdms to morphine had no effect on tumor necrosis factor alpha secretion. Morphine had no effect on later stages of viral replication in HIV-infected h-mdms. Morphine had a potentially additive effect on the HIV-induced production of IL-6 and delayed HIV-induced MCP-2 production. These results suggest that in HIV-infected opiate-abusers, enhanced CNS inflammation might result even when HIV disease is controlled. 相似文献
17.
18.
Gautam Sharma Nagendra Boopathy Senguttuvan Sandeep Singh Rajnish Juneja Vinay K Bahl 《Indian pacing and electrophysiology journal》2012,12(6):274-277
Central venous stenosis after the insertion of a permanent pacemaker is a well recognized complication. This late complication is encountered when there is a need to change the pacemaker lead or extract it. We describe a young male who had such a complication after many years after right side pacemaker implantation. The lesion was managed percutaneously leading to placement of a new lead from the left side. 相似文献
19.
Veerapathran A Joshi R Goswami K Dogra S Moodie EE Reddy MV Kalantri S Schwartzman K Behr MA Menzies D Pai M 《PloS one》2008,3(3):e1850
Background
Although interferon-gamma release assays (IGRA) are promising alternatives to the tuberculin skin test, interpretation of repeated testing results is hampered by lack of evidence on optimal cut-offs for conversions and reversions. A logical start is to determine the within-person variability of T-cell responses during serial testing.Methodology/Principal Findings
We performed a pilot study in India, to evaluate the short-term reproducibility of QuantiFERON-TB Gold In Tube assay (QFT) among 14 healthcare workers (HCWs) who underwent 4 serial QFT tests on day 0, 3, 9 and 12. QFT ELISA was repeated twice on the same sets of specimens. We assessed two types of reproducibility: 1) test-retest reproducibility (between-test variability), and 2) within-person reproducibility over time. Test-retest reproducibility: with dichotomous test results, extremely high concordance was noticed between two tests performed on the same sets of specimens: of the 56 samples, the test and re-test results agreed for all but 2 individuals (κ = 0.94). Discordance was noted in subjects who had IFN-γ values around the cut-off point, with both increases and decreases noted. With continuous IFN-γ results, re-test results tended to produce higher estimates of IFN-γ than the original test. Within-person reproducibility: when continuous IFN-γ data were analyzed, the within-person reproducibility was moderate to high. While persons with negative QFT results generally stayed negative, positive results tended to vary over time. Our data showed that increases of more than 16% in the IFN-γ levels are statistically improbable in the short-term.Conclusions
Conservatively assuming that long-term variability might be at least twice higher than short-term, we hypothesize that a QFT conversion requires two conditions to be met: 1) change from negative to positive result, and 2) at least 30% increase in the baseline IFN-γ response. Larger studies are needed to confirm our preliminary findings, and determine the conversion thresholds for IGRAs. 相似文献20.
Karl E. Andersson George S. Drummond Umberto Freddara Mohinder K. Sardana Shigeru Sassa 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,676(3):289-299
The effects of single large doses of the porphyrin-heme precursor ?d-aminolevulinic acid on tissue porphyrins and on δ-aminolevulinate synthase and heme oxygenase, the rate-living enzymes of liver heme synthesis and degradation respectively, were studied in the chick embryo in ovo, in the mouse and in the rat. δ-Aminolevulinic acid treatment produced a distinctive pattern characterized by extensive tissue porphyrin accumulation and alterations in these rate-limiting enzymes in the liver. Repression of basal or allylisopropylacetamide-induced liver δ-aminolevulinate synthase was observed and, in the mouse and the rat, induction of liver heme oxygenase after δ-aminolevulinic acid treatment, in a manner similar to the known effects of hemin on these enzymes. In the chick embryo liver in ovo heme oxygenase was substantially higher than in rat and mouse liver, and was not significantly induced by δ-aminolevulinic acid or other compounds, including hemin, CS2 and CoCl2. Levulinic acid, an analogue of δ-aminolevulinic acid, did not induce heme oxygenase in mouse liver. δ-Aminolevunilic acid treatment did not impair ferrochelatase activity but was associated with slight and variable decreases in liver cytochrome P-450. Treatment of chick embryos with a small ‘priming’ dose of 1,4-dihydro-3,5-dicarbethoxycollidine, which impairs liver ferrochelatase activity, accentuated porphyrin accumulation after δ-aminolevulinic acid in the liver. These observations indicate that exogenous δ-aminolevulinic acid is metabolized to porphyrins in a number of tissues and, at least in the liver, to a physiologically significant amount of heme, thereby producing an increase in the size of one or more of the heme pools that regulate both heme systhesis and degradation. It is also possible than when δ-aminolevulinic acid is markedly overproduced in vivo it may be transported to many tissues and re-enter the heme pathway and alter porphyrin-heme metabolism in cells and tissues other than those in which its overproduction primarily occurs. 相似文献