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91.
Devasahayam J. Christopher Peter Daley Lois Armstrong Prince James Richa Gupta Beulah Premkumar Joy Sarojini Michael Vedha Radha Alice Zwerling Ian Schiller Nandini Dendukuri Madhukar Pai 《PloS one》2010,5(4)
Background
Among healthcare workers in developing countries, nurses spend a large amount of time in direct contact with tuberculosis (TB) patients, and are at high risk for acquisition of TB infection and disease. To better understand the epidemiology of nosocomial TB among nurses, we recruited a cohort of young nursing trainees at Christian Medical College, a large, tertiary medical school hospital in Southern India.Methodology/Principal Findings
Among 535 nursing students enrolled in 2007, 468 gave consent to participate, and 436 underwent two-step tuberculin skin testing (TST). A majority (95%) were females, and almost 80% were under 22 years of age. Detailed TB exposure information was obtained using interviews and clinical log books. Prevalence of latent TB infection (LTBI) was estimated using Bayesian latent class analyses (LCA). Logistic regression analyses were done to determine the association between LTBI prevalence and TB exposure and risk factors. 219 of 436 students (50.2%, 95% CI: 45.4–55.0) were TST positive using the 10 mm or greater cut-off. Based on the LCA, the prevalence of LTBI was 47.8% (95% credible interval 17.8% to 65.6%). In the multivariate analysis, TST positivity was strongly associated with time spent in health care, after adjusting for age at entry into healthcare.Conclusions
Our study showed a high prevalence of LTBI even in young nursing trainees. With the recent TB infection control (TBIC) policy guidance from the World Health Organization as the reference, Indian healthcare providers and the Indian Revised National TB Control Programme will need to implement TBIC interventions, and enhance capacity for TBIC at the country level. Young trainees and nurses, in particular, will need to be targeted for TBIC interventions. 相似文献92.
Thirunavukkarasu C Premkumar K Sheriff AK Sakthisekaran D 《Molecular and cellular biochemistry》2008,310(1-2):129-139
An element/compound that acts as an antioxidant as well as, can increase the oxidative stress offers a new approach in differentiation
therapy. Experiments were carried out to determine the effect of selenite on DNA damage and glutathione peroxidase (GPx) activity
in N-nitrosodiethylamine (DEN) induced, phenobarbital promoted rat hepatoma. Supra-nutritional level of selenite (4 ppm) was
supplemented at either, before-initiation/after-initiation and/or during entire period of the study. At the end of experiment
period (20 weeks), extent of DNA damage (alkaline comet assay), selenium concentration, and GPx activity were assessed on
nodular tissue (NL) cells, surrounding liver (SL) cells, and whole liver tissue (control) cells. Hepatic selenium level and
GPx activity were decreased in DEN and PB-administered animals, whereas the DNA damage was found to be increased in both NL
and SL cells compared with control group. However, the DNA damage is more in SL cells than in NL cells. Pre-supplementation
of selenite did not show any difference in DNA (strand breaks) damage, selenium, and GPx activity. Increased hepatic selenium
concentration and GPx activity were observed in both NL and SL cells in post-supplementation and entire period of selenite
supplemented animals compared to DEN + PB treated animals. However, DNA damage was increased in NL but decreased in SL cells.
Supplementation of selenite alone for 16 or 20 weeks had shown increased DNA damage, selenium concentration, and GPx activity
compared to normal control animals. In summary, cancer bearing animals increased DNA damage and decreased Se level and GPx
activity in NL and SL cells and other organs in cancer bearing animals, supplementation of Se further provoked DNA damage
(no change in pretreatment) in NL cells, however it decreased DNA damage SL cells and other organs (kidney, lungs, and spleen).
On the other hand Se levels and GPx activity were increased in NL and SL cells and other organs of Se-supplemented rats (no
difference in group 3 animals). These results demonstrate that, in addition to chemopreventive and chemotherapeutic role of
selenite, it also prevents cellular DNA damage induced in cancerous condition. 相似文献
93.
Properties of exogenously added GPI-anchored proteins following their incorporation into cells. 总被引:7,自引:0,他引:7
D R Premkumar Y Fukuoka D Sevlever E Brunschwig T L Rosenberry M L Tykocinski M E Medof 《Journal of cellular biochemistry》2001,82(2):234-245
Isolated glycosylphosphatidylinositol (GPI)-anchored proteins, when added to cells in vitro, incorporate into their surface membranes and, once incorporated, exert their native functions. Virtually any protein of interest, if expressed as a GPI-reanchored derivative, can be modified to acquire this capacity. Such transfer of proteins directly to cells, termed "protein engineering" or "painting" constitutes an alternative to conventional gene transfer for manipulating cell surface composition that has many potential applications. Previous studies with incorporated GPI-anchored proteins have focused almost entirely on their extracellular functions. In this study, biotinylated human erythrocyte (E(hu)) decay accelerating factor, E(hu) acetylcholinesterase, and GPI-reanchored murine B7-1 and B7-2 were used as GPI-anchored reporters to characterize their plasma membrane organization and cell signalling properties following addition to Hela or Chinese hamster ovary cells. For each reporter, three types of cell-association were documented; (1) nonphysiological attachment and/or incomplete insertion, (2) uncomplexed membrane integration, and (3) organization into TX-100-resistant microdomains. Transit from the first two compartments into the third, i.e., microdomains, progressed slowly, continuing even after 24 to 36 h and was associated with the acquisition of cell signalling capacity. All four reporters, incorporated in two different detergents, behaved similarly. When organized in microdomains, caveolin and other GPI proteins co-isolated with the incorporated reporter. These results have implications for protein engineering of cells in general, and in particular, for cells such as modified tumor cell immunogens administered to patients for therapeutic purposes. 相似文献
94.
Dehaye JP Nagy A Premkumar A Turner RJ 《The Journal of biological chemistry》2003,278(14):11811-11817
The secretory Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is a member of a small gene family of electroneutral salt transporters that play essential roles in salt and water homeostasis in many mammalian tissues. We have identified a highly conserved residue (Ala-483) in the sixth membrane-spanning segment of rat NKCC1 that when mutated to cysteine renders the transporter sensitive to inhibition by the sulfhydryl reagents 2-aminoethyl methanethiosulfonate (MTSEA) and 2-(trimethylammonium)ethyl methanethiosulfonate (MTSET). The mutation of Ala-483 to cysteine (A483C) results in little or no change in the affinities of NKCC1 for substrate ions but produces a 6-fold increase in sensitivity to the inhibitor bumetanide, suggesting a specific modification of the bumetanide binding site. When residues surrounding Ala-483 were mutated to cysteine, only I484C was sensitive to inhibition by MTSEA and MTSET. Surprisingly I484C showed increased transport activity in the presence of low concentrations of mercury (1-10 microm), whereas A483C showed inhibition. The inhibition of A483C by MTSEA was unaffected by the presence or absence of sodium and potassium but required the presence of extracellular chloride. Taken together, our results indicate that Ala-483 lies at or near an important functional site of NKCC1 and that the exposure of this site to the extracellular medium is dependent on the conformation of the transporter. Specifically, our results indicate that the cysteine introduced at residue 483 is only available for interaction with MTSEA when chloride is bound to NKCC1 at the extracellular surface. 相似文献
95.
Dinadayala P Laval F Raynaud C Lemassu A Laneelle MA Laneelle G Daffe M 《The Journal of biological chemistry》2003,278(9):7310-7319
Disruption of the mma4 gene (renamed hma) of Mycobacterium tuberculosis has yielded a mutant strain defective in the synthesis of both keto- and methoxymycolates, with an altered cell-wall permeability to small molecules and a decreased virulence in the mouse model of infection (Dubnau, E., Chan, J., Raynaud, C., Mohan, V. P., Lanéelle, M. A., Yu, K., Quémard, A., Smith, I., and Daffé, M. (2000) Mol. Microbiol. 36, 630-637). Assuming that the mutant would accumulate the putative precursors of the oxygenated mycolates of M. tuberculosis, a detailed structural analysis of mycolates from the hma-inactivated strain was performed using a combination of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, proton NMR spectroscopy, and chemical degradation techniques. These consisted most exclusively of alpha-mycolates, composed of equal amounts of C(76)-C(82) dicyclopropanated (alpha(1)) and of C(77)-C(79) monoethylenic monocyclopropanated (alpha(2)) mycolates, the double bond being located at the "distal" position. In addition, small amounts of cis-epoxymycolates, structurally related to alpha(2)-mycolates, was produced by the mutant strain. Complementation of the hma-inactivated mutant with the wild-type gene resulted in the disappearance of the newly identified mycolates and the production of keto- and methoxymycolates of M. tuberculosis. Introduction of the hma gene in Mycobacterium smegmatis led to the lowering of diethylenic alpha mycolates of the recipient strain and the production of keto- and hydroxymycolates. These data indicate that long-chain ethylenic compounds may be the precursors of the oxygenated mycolates of M. tuberculosis. Because the lack of production of several methyltransferases involved in the biosynthesis of mycolates is known to decrease the virulence of the tubercle bacillus, the identification of the substrates of these enzymes should help in the design of inhibitors of the growth of M. tuberculosis. 相似文献
96.
T.?Premkumar S.?GovindarajanEmail author 《World journal of microbiology & biotechnology》2005,21(4):479-480
Summary Some new hydrazinium salts of 2-pyrazinecarboxylate, 2,3-pyrazinedicarboxylate, 3,5-pyrazoledicarboxylate and 4,5-imidazoledicarboxylate have been prepared. The in vitro antibacterial screening of the free acids and their hydrazinium salts has been carried out against Escherichia coli, Salmonella typhiiand Vibrio cholerae. The antibacterial activities of the prepared hydrazinium salts show more promising activity than the corresponding free acids and the standard positive control antibiotic, Co-trimoxazole. 相似文献
97.
Studies on the synthesis,characterization, human serum albumin binding and biological activity of single chain surfactant–cobalt(III) complexes
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G. Vignesh K. Sugumar S. Arunachalam S. Vignesh R. Arthur James R. Arun K. Premkumar 《Luminescence》2016,31(2):523-532
The interaction of surfactant–cobalt(III) complexes [Co(bpy)(dien)TA](ClO4)3 · 3H2O (1) and [Co(dien)(phen)TA](ClO4)3 · 4H2O (2), where bpy = 2,2′‐bipyridine, dien = diethylenetriamine, phen = 1,10‐phenanthroline and TA = tetradecylamine with human serum albumin (HSA) under physiological conditions was analyzed using steady state, synchronous, 3D fluorescence, UV/visabsorption and circular dichroism spectroscopic techniques. The results show that these complexes cause the fluorescence quenching of HSA through a static mechanism. The binding constant (Kb) and number of binding‐sites (n) were obtained at different temperatures. The corresponding thermodynamic parameters (?G°, ?H° and ?S°) and Ea were also obtained. According to Förster's non‐radiation energy transfer theory, the binding distance (r) between the complexes and HSA were calculated. The results of synchronous and 3D fluorescence spectroscopy indicate that the binding process has changed considerably the polarity around the fluorophores, along with changes in the conformation of the protein. The antimicrobial and anticancer activities of the complexes were tested and the results show that the complexes have good activities against pathogenic microorganisms and cancer cells. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
98.
J. P. Curmi L. S. Premkumar B. Birnir P. W. Gage 《The Journal of membrane biology》1993,136(3):273-280
Chloride currents were activated by a low concentration of GABA (0.5
m) in neonatal rat hippocampal neurons cultured for up to 14 days. Currents elicited by 0.5
m GABA in neurons, voltage-clamped using the whole-cell technique with pipettes containing 149 mm Cl–, reversed close to 0 mV whether pipettes contained 144 mm Na+ or 140 mm Cs+, and were blocked by 100
m bicuculline. Current-voltage curves showed outward rectification. Single channel currents appeared in cell-attached patches when the pipette tip was perfused with pipette solution containing 0.5
m GABA and disappeared when a solution containing 100
m bicuculline plus 0.5
m GABA was injected into the pipette tip. The channels showed outward rectification and, in some patches, had a much lower probability of opening at hyperpolarized potentials. The average chord conductance in 10 patches hyperpolarized by 80 mV was 7.8±1.6 pS (sem) compared with a chord conductance of 34.1±3.5 pS (sem) in the same patches depolarized by 80 mV. Similar single channel currents were also activated in cell-free, inside-out patches in symmetrical chloride solutions when 0.5
m GABA was injected into the pipette tip. The channels showed outward rectification similar to that seen in cell-attached patches, and some channels had a lower probability of opening at hyperpolarized potentials. The average chord conductance in 13 patches hyperpolarized by 80 mV was 11.8±2.3 pS (sem) compared with 42.1±3.1 pS (sem) in the same patches depolarized by 80 mV.We are grateful to B. McLachlan and M. Robertson for their general assistance, to C. McCulloch and M. Smith for writing computer programs and to W. O'Hare for making the pipette injection device. 相似文献
99.
GABA-induced potassium channels in cultured neurons 总被引:3,自引:0,他引:3
L S Premkumar S H Chung P W Gage 《Proceedings. Biological sciences / The Royal Society》1990,241(1301):153-158
When gamma-aminobutyric acid (GABA) or baclofen were applied to cultured rat hippocampal neurons, single-channel potassium currents appeared after a delay of 30 s or more in patches of membrane on the cell surface isolated from the agonists by the recording pipette. The appearance of currents in patches not exposed to agonist, the delay in their appearance and the suppression of currents in cells pre-incubated with pertussis toxin indicate the involvement of an intracellular second messenger system. The channels were associated with a GABAB receptor rather than a GABAA receptor as they were blocked by baclofen, a GABAB antagonist, but were not affected by bicuculline, a GABAA antagonist. A feature of the single channel currents was their variable amplitude: they had a maximum conductance of ca. 70 pS and displayed many lower conductance states that were integral multiples of 5-6 pS. In several cells exposed to GABA or baclofen, first small currents and then progressively larger currents appeared: current amplitude was a multiple of an elementary current. It is suggested that binding of GABA to GABAB receptors activates a second messenger system causing opening of oligomeric potassium channels. 相似文献
100.
N.A. Sunstrom L.S. Premkumar A. Premkumar G. Ewart G.B. Cox P.W. Gage 《The Journal of membrane biology》1996,150(2):127-132
The influenza B virus protein, NB, was expressed in Escherichia coli, either with a C-terminal polyhistidine tag or with NB fused to the C-terminus of glutathione S-transferase (GST), and purified
by affinity chromatography. NB produced ion channel activity when added to artificial lipid bilayers separating NaCl solutions
with unequal concentrations (150–500 mm
cis, 50 mm
trans). An antibody to a peptide mimicking the 25 residues at the C-terminal end of NB, and amantadine at high concentration (2–3
mm), both depressed ion channel activity. Ion channels had a variable conductance, the lowest conductance observed being approximately
10 picosiemens. At a pH of 5.5 to 6.5, currents reversed at positive potentials indicating that the channel was more permeable
to sodium than to chloride ions (PNa/PCl∼ 9). In asymmetrical NaCl solutions at a pH of 2.5, currents reversed closer to the chloride than to the sodium equilibrium
potential indicating that the channel had become more permeable to chloride than to sodium ions (PCl/PNa∼ 4). It was concluded that, at normal pHs, NB forms cation-selective channels.
Received: 6 March 1995/Revised: 17 November 1995 相似文献