全文获取类型
收费全文 | 107篇 |
免费 | 18篇 |
专业分类
125篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 3篇 |
2019年 | 3篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 7篇 |
2013年 | 10篇 |
2012年 | 8篇 |
2011年 | 6篇 |
2010年 | 4篇 |
2009年 | 4篇 |
2008年 | 3篇 |
2007年 | 7篇 |
2006年 | 5篇 |
2005年 | 1篇 |
2003年 | 1篇 |
2002年 | 2篇 |
2001年 | 1篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1995年 | 4篇 |
1991年 | 1篇 |
1989年 | 5篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1975年 | 1篇 |
排序方式: 共有125条查询结果,搜索用时 0 毫秒
41.
Postnatal ethanol exposure alters levels of 2‐arachidonylglycerol‐metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice 下载免费PDF全文
Shivakumar Subbanna Delphine Psychoyos Shan Xie Balapal S. Basavarajappa 《Journal of neurochemistry》2015,134(2):276-287
The consumption of ethanol by pregnant women may cause neurological abnormalities, affecting learning and memory processes in children, and are collectively described as fetal alcohol spectrum disorders. However, the molecular mechanisms underlying these changes are still poorly understood. In our previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice significantly enhances the anandamide levels but not the 2‐arachidonylglycerol (2‐AG) levels and induces widespread neurodegeneration, but the reason for the lack of significant effects of ethanol on the 2‐AG level is unknown. In this study, we examined developmental changes in diacylglycerol lipase‐α, β (DAGL‐α and β) and monoacylglycerol lipase (MAGL). We found that the levels of these proteins were significantly higher in adult brains compared to those detected early in brain development. Next, we examined the influence of P7 ethanol treatment on these enzymes, finding that it differentially altered the DAGL‐α protein and mRNA levels but consistently enhanced those of the DAGL‐β. Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels. Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice. Collectively, these findings suggest that ethanol significantly activates DAGL‐β and MAGL in the neonatal brain, resulting in no net change in 2‐AG levels.
42.
CB1‐receptor knockout neonatal mice are protected against ethanol‐induced impairments of DNMT1, DNMT3A,and DNA methylation 下载免费PDF全文
Nagaraja N. Nagre Shivakumar Subbanna Madhu Shivakumar Delphine Psychoyos Balapal S. Basavarajappa 《Journal of neurochemistry》2015,132(4):429-442
The significant consequences of ethanol use during pregnancy are neurobehavioral abnormalities involving hippocampal and neocortex malfunctions that cause learning and memory deficits collectively named fetal alcohol spectrum disorder. However, the molecular mechanisms underlying these abnormalities are still poorly understood and therefore warrant systematic research. Here, we document novel epigenetic abnormalities in the mouse model of fetal alcohol spectrum disorder. Ethanol treatment of P7 mice, which induces activation of caspase 3, impaired DNA methylation through reduced DNA methyltransferases (DNMT1 and DNMT3A) levels. Inhibition of caspase 3 activity, before ethanol treatment, rescued DNMT1, DNMT3A proteins as well as DNA methylation levels. Blockade of histone methyltransferase (G9a) activity or cannabinoid receptor type‐1 (CB1R), prior to ethanol treatment, which, respectively, inhibits or prevents activation of caspase 3, rescued the DNMT1 and DNMT3A proteins and DNA methylation. No reduction of DNMT1 and DNMT3A proteins and DNA methylation was found in P7 CB1R null mice, which exhibit no ethanol‐induced activation of caspase 3. Together, these data demonstrate that ethanol‐induced activation of caspase 3 impairs DNA methylation through DNMT1 and DNMT3A in the neonatal mouse brain, and such impairments are absent in CB1R null mice. Epigenetic events mediated by DNA methylation may be one of the essential mechanisms of ethanol teratogenesis.
43.
Roshan Singh Thakur Ambika Desingu Shivakumar Basavaraju Shreelakshmi Subramanya Desirazu N. Rao Ganesh Nagaraju 《The Journal of biological chemistry》2014,289(36):25112-25136
The significance of G-quadruplexes and the helicases that resolve G4 structures in prokaryotes is poorly understood. The Mycobacterium tuberculosis genome is GC-rich and contains >10,000 sequences that have the potential to form G4 structures. In Escherichia coli, RecQ helicase unwinds G4 structures. However, RecQ is absent in M. tuberculosis, and the helicase that participates in G4 resolution in M. tuberculosis is obscure. Here, we show that M. tuberculosis DinG (MtDinG) exhibits high affinity for ssDNA and ssDNA translocation with a 5′ → 3′ polarity. Interestingly, MtDinG unwinds overhangs, flap structures, and forked duplexes but fails to unwind linear duplex DNA. Our data with DNase I footprinting provide mechanistic insights and suggest that MtDinG is a 5′ → 3′ polarity helicase. Notably, in contrast to E. coli DinG, MtDinG catalyzes unwinding of replication fork and Holliday junction structures. Strikingly, we find that MtDinG resolves intermolecular G4 structures. These data suggest that MtDinG is a multifunctional structure-specific helicase that unwinds model structures of DNA replication, repair, and recombination as well as G4 structures. We finally demonstrate that promoter sequences of M. tuberculosis PE_PGRS2, mce1R, and moeB1 genes contain G4 structures, implying that G4 structures may regulate gene expression in M. tuberculosis. We discuss these data and implicate targeting G4 structures and DinG helicase in M. tuberculosis could be a novel therapeutic strategy for culminating the infection with this pathogen. 相似文献
44.
Therapeutic options for infections caused by gram-negative organisms expressing plasmid-mediated AmpC β-lactamases are limited because these organisms are usually resistant to all the β-lactam antibiotics, except for cefepime, cefpirome and the carbapenems. These organisms are a major concern in nosocomial infections and should therefore be monitored in surveillance studies. Hence, this study was aimed out to determine the prevalence of plasmid-mediated AmpC β-lactamases in E. coli and K. pneumoniae from a tertiary care in Bangalore. A total of 63 E. coli and 27 K. pneumoniae were collected from a tertiary care hospital in Bangalore from February 2008 to July 2008. The isolates with decreased susceptibility to cefoxitin were subjected to confirmation test with three dimensional extract tests. Minimum inhibitory concentrations (MICs) were determined by agar dilution method. Conjugation experiments, plasmid profiling and susceptibility testing were carried out to investigate the underlying mechanism of resistance. In our study, 52 (57.7%) isolates showed resistance to cefoxitin, the occurrence of AmpC was found to be 7.7% of the total isolates. Plasmid analysis of the selected isolates showed the presence of a single plasmid of 26 kb in E. coli and 2 Kb in K. pneumoniae. Plasmid-mediated AmpC β-lactamases were found in 11.1% of K. pneumoniae and in 6.3% of E. coli. Curing and conjugation experiments showed that resistance to cephamycins and cephalosporins was plasmid-mediated. Our study has demonstrated the occurrence of plasmid-mediated AmpC in E. coli and K. pneumoniae which illustrates the importance of molecular surveillance in tracking AmpC-producing strains at general hospitals and emphasizes the need for epidemiological monitoring. 相似文献
45.
46.
Significant differences in expression of the delta-endotoxin genes cryA1 and cryA2 of Bacillus thuringiensis subsp. kurstaki were observed in B. subtilis and B. megaterium. The cryA1 gene was expressed when present on a high-copy-number (hcn) vector in B. megaterium but not in B. subtilis. The cryA2 gene was expressed in both hosts, but at a higher level in B. megaterium. Expression of the cryA2 gene in B. megaterium was better from a hcn vector than from a low copy number vector. Inhibition of sporulation was observed when the toxin genes were present on hcn plasmids in B. subtilis while no such effect was evident in B. megaterium. In addition, there was a significant reduction in copy numbers in both B. subtilis and B. megaterium when delta-endotoxin genes or a spoVG promoter-containing fragment of DNA were cloned into hcn plasmids. 相似文献
47.
Chandrashekar Unnenahally Shivakumar Ramwant Gupta Manjunath Prasad Cholanayakanahalli Thyagaraju Shyamal Kumar Chakrabarty Malavika Dadlani 《Grana》2013,52(2):103-110
The pollen morphology of two species of Drosera has been investigated by means of both light and electron microscopy. The apertures are situated proximally, a state rarely found in the pollen of Angiospermous plants. The pollen morphology of Aldrovanda, Dionea and Drosophyllum is compared. 相似文献
48.
S Shivakumar G C Tsokos S K Datta 《Journal of immunology (Baltimore, Md. : 1950)》1989,143(1):103-112
It is generally accepted that human Th cells express the surface glycoproteins CD4 and alpha/beta-chain heterodimer of the TCR whereas cytotoxic/suppressor cells are usually CD8+ and alpha/beta TCR+. Another minor set of T cells found in the periphery are CD4-/CD8- (double negative) and express the gamma/delta TCR; these cells can manifest MHC-restricted or nonrestricted cytotoxicity but no helper function. Herein we describe the existence of an unusual Th population in the peripheral blood of humans that are CD4-/CD8- and alpha/beta TCR+. These double-negative Th were markedly expanded in patients with the autoimmune disease SLE and along with CD4+ Th, they induced production of the pathogenic variety of anti-DNA autoantibodies that are IgG in class and cationic in charge. The cationic anti-DNA antibodies induced by the Th were markedly restricted in spectrotype indicating that an oligoclonal population of B cells were committed to produce the pathogenic autoantibodies in active lupus. IL-2-dependent T cell lines were also derived from the patients with active lupus nephritis but the majority of those T cell lines lacked pathogenic autoantibody-inducing capability. Only 4 out of 42 T cell lines from a lupus patient could induce the production of cationic IgG class anti-DNA autoantibodies. The phenotypes of the pathogenic autoantibody-inducing Th lines were similar to the Th subsets: CD4+, alpha/beta TCR+ or CD4-/CD8-, alpha/beta TCR+. These studies suggest that production of pathogenic autoantibodies in human lupus is mediated by mechanisms that are distinct from the generalized, nonspecific polyclonal B cell hyperactivity that leads to excessive production of natural autoantibodies. 相似文献
49.
Kadallipura Puttaswamy Rakesh Suhas Ramesh Shivakumar Dase Channe Gowda 《Russian Journal of Bioorganic Chemistry》2018,44(2):158-164
Peptides of relatively low charge and a high number of hydrophobic amino acids were designed. The amino acid sequence of designed peptides was GXGVP, where X equaled to W, Y, F, D, and T with a combination of hydrophobic, charged and polar units. These peptides were linked to quinazolinones to obtain a new class of compounds with synergistic features. The hybrids displayed antimicrobial activity against Gram-positive and Gram-negative bacteria. In particular, Trp, Tyr, and Phe-containing peptides showed greater antimicrobial potency than the reference standards. Alkyl chain length variations in heterocyclic moiety indicated that hybrids with propyl group were more active than butyl derivatives. Improved results were observed for debenzylated versions of the conjugates compared to their benzylated counterparts. Implementation of the hybrid structures of varying charge, hydrophobicity, and alkyl chain length would be a promising approach to obtaining effective antimicrobial agents. 相似文献
50.
Jason E. Miller Manu K. Shivakumar Younghee Lee Seonggyun Han Emrin Horgousluoglu Shannon L. Risacher Andrew J. Saykin Kwangsik Nho Dokyoon Kim for the Alzheimer’s Disease Neuroimaging Initiative 《BMC medical genomics》2018,11(3):76