全文获取类型
收费全文 | 344篇 |
免费 | 22篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 8篇 |
2015年 | 14篇 |
2014年 | 17篇 |
2013年 | 28篇 |
2012年 | 22篇 |
2011年 | 10篇 |
2010年 | 7篇 |
2009年 | 12篇 |
2008年 | 10篇 |
2007年 | 13篇 |
2006年 | 10篇 |
2005年 | 10篇 |
2004年 | 9篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1992年 | 7篇 |
1991年 | 12篇 |
1990年 | 8篇 |
1989年 | 13篇 |
1988年 | 11篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 9篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1972年 | 3篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1968年 | 2篇 |
1967年 | 4篇 |
排序方式: 共有366条查询结果,搜索用时 15 毫秒
31.
The receptor for phage M-1 was present in the exopolysaccharide (EPS) of Rhizobium japonicum D211. The EPS was a heteropolysaccharide consisting of glucose, galactose, glucuronic acid, and glucosamine units. These monosaccharides prevented phage-cell attachment indicating that they may mimick the receptor. Phage-cell attachment was either stimulated or inhibited by Mg2+ and Ca2+ depending upon their concentration. An enzyme which depolymerized the exopolysaccharide releasing oligosaccharides was detected in the phage-infected cell lysates. A comparison of the properties of adsorption and those of the depolymerase enzyme indicated that the latter was a component of the phage and appeared to be involved in the phage-receptor interaction. 相似文献
32.
Fructose-1,6-diphosphatase (FDPase) from unripe mango was separated into two components by ammonium sulfate fractionation, one active at pH 6 (acidic FDPase) and the other at pH 8.5 (alkaline FDPase). The alkaline component had a lower Km. (0.15 × 10?3 M) than the acidic component (1.7 × 10?3 M) towards the substrate (FDP) and the allosteric inhibitor AMP. It also showed greater heat stability and higher activation in the presence of EDTA as compared to the acidic FDPase. Both components showed a higher activation with Mn2+ ions than with Mg2+ ions. 相似文献
33.
Spectrophotometric observations on verdo-myoglobin, reconstituted from apomyoglobin and verdo-heme and its oxidation products, are described. Relevance of these results to the oxidation of ferri-myoglobin by chlorite ion is also discussed. 相似文献
34.
Anubhuti Dixit Anjali Sandhu Souvik Modi Meghana Shashikanth Sandhya P. Koushika Jennifer L. Watts Varsha Singh 《Aging cell》2020,19(6)
The G protein‐coupled receptor (GPCR) encoding family of genes constitutes more than 6% of genes in Caenorhabditis elegans genome. GPCRs control behavior, innate immunity, chemotaxis, and food search behavior. Here, we show that C. elegans longevity is regulated by a chemosensory GPCR STR‐2, expressed in AWC and ASI amphid sensory neurons. STR‐2 function is required at temperatures of 20°C and higher on standard Escherichia coli OP50 diet. Under these conditions, this neuronal receptor also controls health span parameters and lipid droplet (LD) homeostasis in the intestine. We show that STR‐2 regulates expression of delta‐9 desaturases, fat‐5, fat‐6 and fat‐7, and of diacylglycerol acyltransferase dgat‐2. Rescue of the STR‐2 function in either AWC and ASI, or ASI sensory neurons alone, restores expression of fat‐5, dgat‐2 and restores LD stores and longevity. Rescue of stored fat levels of GPCR mutant animals to wild‐type levels, with low concentration of glucose, rescues its lifespan phenotype. In all, we show that neuronal STR‐2 GPCR facilitates control of neutral lipid levels and longevity in C. elegans. 相似文献
35.
Chirag N. Patel Sivakumar Prasanth Kumar Krunal M. Modi Mehul N. Soni Nainesh R. Modi 《Journal of receptor and signal transduction research》2013,33(3):226-234
AbstractCardiotonic steroids (CTS) are steroidal drugs, processed from the seeds and dried leaves of the genus Digitalis as well as from the skin and parotid gland of amphibians. The most commonly known CTS are ouabain, digoxin, digoxigenin and bufalin. CTS can be used for safer medication of congestive heart failure and other related conditions due to promising pharmacological and medicinal properties. Ouabain isolated from plants is widely utilized in in vitro studies to specifically block the sodium potassium (Na+/K+-ATPase) pump. For checking, whether ouabain derivatives are robust inhibitors of Na+/K+-ATPase pump, molecular docking simulation was performed between ouabain and its derivatives using YASARA software. The docking energy falls within the range of 8.470?kcal/mol to 7.234?kcal/mol, in which digoxigenin was found to be the potential ligand with the best docking energy of 8.470?kcal/mol. Furthermore, pharmacophore modeling was applied to decipher the electronic features of CTS. Molecular dynamics simulation was also employed to determine the conformational properties of Na+/K+-ATPase-ouabain and Na+/K+-ATPase-digoxigenin complexes with the plausible structural integrity through conformational ensembles for 100?ns which promoted digoxigenin as the most promising CTS for treating conditions of congestive heart failure patients. 相似文献
36.
Hiren R. Modi Mireille Basselin Ameer Y. Taha Lei O. Li Rosalind A. Coleman Meir Bialer Stanley I. Rapoport 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(4):880-886
Background
Mood stabilizers used for treating bipolar disorder (BD) selectively downregulate arachidonic acid (AA) turnover (deacylation–reacylation) in brain phospholipids, when given chronically to rats. In vitro studies suggest that one of these, valproic acid (VPA), which is teratogenic, reduces AA turnover by inhibiting the brain long-chain acyl-CoA synthetase (Acsl)4 mediated acylation of AA to AA-CoA. We tested whether non-teratogenic VPA analogues might also inhibit Acsl4 catalyzed acylation, and thus have a potential anti-BD action.Methods
Rat Acsl4-flag protein was expressed in Escherichia coli, and the ability of three VPA analogues, propylisopropylacetic acid (PIA), propylisopropylacetamide (PID) and N-methyl-2,2,3,3-tetramethylcyclopropanecarboxamide (MTMCD), and of sodium butyrate, to inhibit conversion of AA to AA-CoA by Acsl4 was quantified using Michaelis–Menten kinetics.Results
Acsl4-mediated conversion of AA to AA-CoA in vitro was inhibited uncompetitively by PIA, with a Ki of 11.4 mM compared to a published Ki of 25 mM for VPA, while PID, MTMCD and sodium butyrate had no inhibitory effect.Conclusions
PIA's ability to inhibit conversion of AA to AA-CoA by Acsl4 in vitro suggests that, like VPA, PIA may reduce AA turnover in brain phospholipids in unanesthetized rats, and if so, may be effective as a non-teratogenic mood stabilizer in BD patients. 相似文献37.
Andrew M. Steffensmeier Meghana Tare Oorvashi Roy Puli Rohan Modi Jaison Nainaparampil Madhuri Kango-Singh Amit Singh 《PloS one》2013,8(11)
Alzheimer''s disease (AD, OMIM: 104300), a progressive neurodegenerative disorder with no cure to date, is caused by the generation of amyloid-beta-42 (Aβ42) aggregates that trigger neuronal cell death by unknown mechanism(s). We have developed a transgenic Drosophila eye model where misexpression of human Aβ42 results in AD-like neuropathology in the neural retina. We have identified an apical-basal polarity gene crumbs (crb) as a genetic modifier of Aβ42-mediated-neuropathology. Misexpression of Aβ42 caused upregulation of Crb expression, whereas downregulation of Crb either by RNAi or null allele approach rescued the Aβ42-mediated-neurodegeneration. Co-expression of full length Crb with Aβ42 increased severity of Aβ42-mediated-neurodegeneration, due to three fold induction of cell death in comparison to the wild type. Higher Crb levels affect axonal targeting from the retina to the brain. The structure function analysis identified intracellular domain of Crb to be required for Aβ42-mediated-neurodegeneration. We demonstrate a novel neuroprotective role of Crb in Aβ42-mediated-neurodegeneration. 相似文献
38.
Paola Luciani Cristiana Deledda Susanna Benvenuti Roberta Squecco Ilaria Cellai Benedetta Fibbi Ilaria Maddalena Marone Corinna Giuliani Giulia Modi Fabio Francini Gabriella Barbara Vannelli Alessandro Peri 《PloS one》2013,8(8)
Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family. For instance, Peptide YY and Vasoactive Intestinal Peptide have been found to affect cell adhesion and migration and our previous data have shown a considerable actin cytoskeleton rearrangement after exendin-4 treatment. However, no data are currently available on the effects of exendin-4 on tumor cell motility. The aim of this study was to investigate the effects of this molecule on cell adhesion, differentiation and migration in two neuroblastoma cell lines, SH-SY5Y and SK-N-AS. We first demonstrated, by Extra Cellular Matrix cell adhesion arrays, that exendin-4 increased cell adhesion, in particular on a vitronectin substrate. Subsequently, we found that this molecule induced a more differentiated phenotype, as assessed by i) the evaluation of neurite-like protrusions in 3D cell cultures, ii) the analysis of the expression of neuronal markers and iii) electrophysiological studies. Furthermore, we demonstrated that exendin-4 reduced cell migration and counteracted anchorage-independent growth in neuroblastoma cells. Overall, these data indicate for the first time that exendin-4 may have anti-tumoral properties. 相似文献
39.
Myles Horton Jayesh Modi Shiel K. Patel Andrew M. Demchuk Mayank Goyal Michael D. Hill Shelagh B. Coutts 《PloS one》2013,8(6)
Background
TIA and minor stroke have a high risk of recurrent stroke. Abnormalities on CT/CTA and MRI predict recurrent events in TIA and minor stroke. However there are many other imaging abnormalities that could potentially predict outcome that have not been assessed in this population. Also the definition of recurrent events used includes deterioration due to stroke progression or recurrent stroke and whether imaging is either of these is not known.Aims
To improve upon the clinical, CT/CTA and MRI parameters that predict recurrent events after TIA and minor stroke by assessing further imaging parameters. Secondary aim was to explore predictors of stroke progression versus recurrent stroke.Methods
510 consecutive TIA and minor stroke patients had CT/CTA and most had MRI. Primary outcome was recurrent events (stroke progression or recurrent stroke) within 90 days. Further imaging parameters were assessed for prediction of recurrent events (combined outcome of stroke progression and recurrent stroke). We also explored predictors of symptom progression versus recurrence individually.Results
36 recurrent events (36/510, 7.1% (95% CI: 5.0–9.6)) including 19 progression and 17 recurrent strokes. On CT/CTA: white matter disease, prior stroke, aortic arch focal plaque≥4 mm, or intraluminal thrombus did not predict recurrent events (progression or recurrent stroke). On MRI: white matter disease, prior stroke, and microbleeds did not predict recurrent events. Parameters predicting the individual outcome of symptom progression included: ongoing symptoms at initial assessment, symptom fluctuation, intracranial occlusion, intracranial occlusion or stenosis, and the CT/CTA metric. No parameter was strongly predictive of a distinct recurrent stroke.Conclusions
There was no imaging parameter that could improve upon our original CT/CTA or MRI metrics to predict the combined outcome of stroke progression or a recurrent stroke after TIA and minor stroke. We are better at using imaging to predict stroke progression rather than recurrent stroke. 相似文献40.