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501.
502.
Crema LM Vendite D Horn AP Diehl LA Aguiar AP Nunes E Vinade L Fontella FU Salbego C Dalmaz C 《Neurochemical research》2009,34(3):499-507
Glutamate is an excitatory neurotransmitter involved in neuronal plasticity and neurotoxicity. Chronic stress produces several
physiological changes on the spinal cord, many of them presenting sex-specific differences, which probably involve glutamatergic
system alterations. The aim of the present study was to verify possible effects of exposure to chronic restraint stress and
17β-estradiol replacement on [3H]-glutamate release and uptake in spinal cord synaptosomes of ovariectomized (OVX) rats. Female rats were subjected to OVX,
and half of the animals received estradiol replacement. Animals were subdivided in controls and chronically stressed. Restraint
stress or estradiol had no effect on [3H]-glutamate release. The chronic restraint stress promoted a decrease and 17β-estradiol induced an increase on [3H]-glutamate uptake, but the uptake observed in the restraint stress +17β-estradiol group was similar to control. Furthermore,
17β-estradiol treatment caused a significant increase in the immunocontent of the three glutamate transporters present in
spinal cord. Restraint stress had no effect on the expression of these transporters, but prevented the 17β-estradiol effect.
We suggest that changes in the glutamatergic system are likely to take part in the mechanisms involved in spinal cord plasticity
following repeated stress exposure, and that 17β-estradiol levels may affect chronic stress effects in this structure. 相似文献
503.
Colabufo NA Berardi F Cantore M Perrone MG Contino M Inglese C Niso M Perrone R Azzariti A Simone GM Porcelli L Paradiso A 《Bioorganic & medicinal chemistry》2008,16(1):362-373
The development of small molecules as P-gp modulating agents and SAR studies on these ligands represented the aim of the present work. A series of 6,7-dimethoxytetrahydroisoquinoline derivatives was prepared and their ability to inhibit P-gp activity has been evaluated. The basic nucleus of these compounds, common to the best P-gp inhibitors such as Tariquidar and Elacridar, has been functionalized with no-basic moiety from our studied sigma receptor ligands displaying potent P-gp inhibition. The best results were obtained for compounds 3c and 3a (EC(50)=1.64 and 4.86 microM, respectively) and these results were remarkable because Elacridar showed in the same biological evaluation similar inhibitory activity (EC(50)=2 microM). SAR studies displayed that the removal of double bond on the spacer or its shifting into tetraline ring decreased the P-gp inhibiting activity. Moreover, the P-gp inhibition mechanism of tested compounds was investigated by three selected biological experiments. The results displayed that only compound 3c was P-gp inhibitor as Elacridar, while compound 3a and reference compounds Cyclosporin A and Verapamil modulated P-gp activity saturating the efflux pump as substrates. Flow cytometry studies carried out in Doxorubicin resistant breast cancer cell line (MCF7/Adr) confirmed that compound 3c increased Doxorubicin cell accumulation 5.7-fold. In addition, in MCF7/Adr, antiproliferative effect of 5 microM Doxorubicin shifted from 5% to 95% when co-administered with compound 3c (20 microM). The present study suggested a new class of small molecules displaying P-gp inhibitor activity differing from reference compounds Elacridar and Tariquidar for a simplified, and in the meantime, efficacious no-basic moiety. 相似文献
504.
Saravana R. K. Murthy Tessi Sherrin Chad Jansen Ingrid Nijholt Michael Robles Amalia M. Dolga Nicolas Andreotti Jean-Marc Sabatier Hans-Guenther Knaus Reinhold Penner Cedomir Todorovic Thomas Blank 《PloS one》2015,10(5)
Small-conductance, Ca2+ activated K+ channels (SK channels) are expressed at high levels in brain regions responsible for learning and memory. In the current study we characterized the contribution of SK2 channels to synaptic plasticity and to different phases of hippocampal memory formation. Selective SK2 antisense-treatment facilitated basal synaptic transmission and theta-burst induced LTP in hippocampal brain slices. Using the selective SK2 antagonist Lei-Dab7 or SK2 antisense probes, we found that hippocampal SK2 channels are critical during two different time windows: 1) blockade of SK2 channels before the training impaired fear memory, whereas, 2) blockade of SK2 channels immediately after the training enhanced contextual fear memory. We provided the evidence that the post-training cleavage of the SK2 channels was responsible for the observed bidirectional effect of SK2 channel blockade on memory consolidation. Thus, Lei-Dab7-injection before training impaired the C-terminal cleavage of SK2 channels, while Lei-Dab7 given immediately after training facilitated the C-terminal cleavage. Application of the synthetic peptide comprising a leucine-zipper domain of the C-terminal fragment to Jurkat cells impaired SK2 channel-mediated currents, indicating that the endogenously cleaved fragment might exert its effects on memory formation by blocking SK2 channel-mediated currents. Our present findings suggest that SK2 channel proteins contribute to synaptic plasticity and memory not only as ion channels but also by additionally generating a SK2 C-terminal fragment, involved in both processes. The modulation of fear memory by down-regulating SK2 C-terminal cleavage might have applicability in the treatment of anxiety disorders in which fear conditioning is enhanced. 相似文献
505.
Amalia Pérez-Jiménez M. Carmen Hidalgo Amalia E. Morales Marta Arizcun Emilia Abellán Gabriel Cardenete 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2009,152(3):314-321
The influence of the dietary macronutrient balance on the intermediary metabolism of common dentex (Dentex dentex L.) was evaluated. Four experimental diets combining high and low levels of macronutrients were formulated. Dentex fed on 43% protein had higher liver and muscle lipid content, corresponding with an increased hepatic G6PDH activity. This “excess” of hepatic lipids at higher protein levels could be used to obtain energy as would be reflected by hepatic HOAD. In the liver, 43% of dietary protein induced higher AlaAT and FBPase activities. Similarly, dentex fed on the P43C28 and P38C28 diets showed an increased hepatic and muscular gluconeogenic pathways (higher FBPase activity) from amino acids (elevated AlaAT) and/or glycerol (elevated GK). However, changes in glycemia were not observed among dietary treatments. At coronary level, the use of lower dietary protein induced an increase in the activity of glycolytic (PK and HK-IV) and lipolytic (HOAD) enzymes. Considering the overall results and the experimental conditions, it could be suggested that dietary protein could be reduced until 38% without affecting negatively the normal physiology of dentex. Moreover, high dietary carbohydrate levels could not be used efficiently by dentex given that gluconeogenesis occurs. 相似文献
506.
Tselios T Kelaidonis K Resvani A Prousalis K Matsoukas J Tsegenidis T 《Protein and peptide letters》2008,15(1):1-5
A convenient solid phase synthesis of a Thrombin Receptor Glycopeptide Mimetic analogue namely, 1-O-Methyl-2-N-{1'-(argininocarbonyl)-4'-[(4'-fluoro)-benzylamido]-cyclohexane}-glucosamine using Fmoc/tBu methodology and the 4-Methoxybenzhydryl bromide resin is described. The synthesized analogue was purified by Reverse Phase High Performance Liquid Chromatography (RP-HPLC) and was identified by Electron Spray Ionization-Mass Spectrometry (ESI-MS) and Nuclear Magnetic Resonance (NMR). The synthetic protocol introduced for the first time successfully the acid sensitive 4-Methoxybenzhydryl bromide resin as a scaffold for the synthesis of glycopeptides resulting in high yield reactions. This synthetic procedure could be a general one for the convenient synthesis of such glyco compounds as the method was used for the first time to glycosylate a non peptide mimetic of an important protein sequence, in particular of the thrombin receptor active site S42FLLR46. 相似文献
507.
508.
509.
Sara Grioni Claudia Agnoli Sabina Sieri Valeria Pala Fulvio Ricceri Giovanna Masala Calogero Saieva Salvatore Panico Amalia Mattiello Paolo Chiodini Rosario Tumino Graziella Frasca Licia Iacoviello Amalia de Curtis Paolo Vineis Vittorio Krogh 《PloS one》2015,10(5)
Background
The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style (espresso and mocha) coffee consumption and CHD risk.Methods
We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids.Results
After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87–1.60) for drinking 1–2 cups/day, 1.37 (95% CI 1.03–1.82) for >2–4 cups/day and 1.52 (95% CI 1.11–2.07) for over 4 cups/day (P trend <0.001) compared to reference (<1 cup/day). Plasma triglycerides, and total, LDL and HDL cholesterol did not vary significantly (ANOVA) with coffee consumption.Conclusion
Consumption of over 2 cups/day of Italian-style coffee is associated with increased CHD risk, but coffee consumption was not associated with plasma lipid changes, so the adverse effect of consumption appears unrelated to lipid profile. 相似文献510.
During macrophage infection Candida albicans expresses differentially several genes whose functions are associated with its survival strategy. Among others, we have isolated CaGS gene, which is homologous to SNF3, a glucose sensor of Saccharomyces cerevisiae. To elucidate its potential role during infection, CaGS has been disrupted and the resulting phenotype analyzed on different solid media. The null mutant lost the ability to form hyphae on a medium with low glucose concentration and serum. Furthermore, this mutant does not disrupt macrophage in in vitro infections. We believe that this putative glucose sensor is involved in hyphal development during macrophage infection. 相似文献