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671.
R. Russo G. D’Agostino G. Mattace Raso C. Avagliano C. Cristiano R. Meli A. Calignano 《Peptides》2012
The neuropeptide oxytocin (OXT) contributes to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Although many authors have reported the analgesic effects of OXT, its mechanism has not been well elucidated. Recently, it has been also hypothesize that OXT, increasing intracellular concentration of calcium, could regulate the production of mediators, like endocannabinoids (eCB). It has been well documented that eCB are able to suppress pain pathways. The present study investigates the effect of OXT in paw carrageenan-induced pain. Intracerebroventricular (icv) administration of OXT, but neither intraperitoneal nor intraplantar route, induces an antihyperalgesic effect increasing paw withdrawal latency to mechanical or thermal stimuli. Our results clearly demonstrate that 3 and 6 h following carrageenan challenge, central administration of OXT (30 ng/mouse) shows a significant antihyperalgesic activity. Moreover, for the first time, we demonstrate that CB1 receptor plays a key role in the antihyperalgesic effect of OXT. In fact our results show CB1 antagonist, but not the specific CB2 antagonist reduce OXT-induced antihyperalgesic effect. In addition, our data show that central OXT administration is able to reduce carrageenan-induced hyperalgesia but does not modify carrageenan-induced paw edema. Finally, using opioid antagonists we confirm an important role of opioid receptors. In conclusion, our experiments suggest that central administration of OXT reduces hyperalgesia induced by intraplantar injection of carrageenan, and this effect may work via cannabinoid and opioid systems. 相似文献
672.
Samit K. Bhattacharya Gary E. Aspnes Scott W. Bagley Markus Boehm Arthur D. Brosius Leonard Buckbinder Jeanne S. Chang Joseph Dibrino Heather Eng Kosea S. Frederick David A. Griffith Matthew C. Griffor Cristiano R.W. Guimarães Angel Guzman-Perez Seungil Han Amit S. Kalgutkar Jacquelyn Klug-McLeod Carmen Garcia-Irizarry Jianke Li Blaise Lippa Xumiao Zhao 《Bioorganic & medicinal chemistry letters》2012,22(24):7523-7529
Previous drug discovery efforts identified classical PYK2 kinase inhibitors such as 2 and 3 that possess selectivity for PYK2 over its intra-family isoform FAK. Efforts to identify more kinome-selective chemical matter that stabilize a DFG-out conformation of the enzyme are described herein. Two sub-series of PYK2 inhibitors, an indole carboxamide–urea and a pyrazole–urea have been identified and found to have different binding interactions with the hinge region of PYK2. These leads proved to be more selective than the original classical inhibitors. 相似文献
673.
Vendruscolo Raquel Guidetti Fagundes Mariane Bittencourt Maroneze Mariana Manzoni do Nascimento Tatiele Casagrande de Menezes Cristiano Ragagnin Barin Juliano Smanioto Zepka Leila Queiroz Jacob-Lopes Eduardo Wagner Roger 《Bioprocess and biosystems engineering》2019,42(5):727-739
Bioprocess and Biosystems Engineering - Environmental factors directly affect the growth and composition of microalgal biomass. Therefore, the present work analyzed the metabolomics (amino acids,... 相似文献
674.
675.
Caramelli D Vernesi C Sanna S Sampietro L Lari M Castrì L Vona G Floris R Francalacci P Tykot R Casoli A Bertranpetit J Lalueza-Fox C Bertorelle G Barbujani G 《Human genetics》2007,122(3-4):327-336
We sampled teeth from 53 ancient Sardinian (Nuragic) individuals who lived in the Late Bronze Age and Iron Age, between 3,430
and 2,700 years ago. After eliminating the samples that, in preliminary biochemical tests, did not show a high probability
to yield reproducible results, we obtained 23 sequences of the mitochondrial DNA control region, which were associated to
haplogroups by comparison with a dataset of modern sequences. The Nuragic samples show a remarkably low genetic diversity,
comparable to that observed in ancient Iberians, but much lower than among the Etruscans. Most of these sequences have exact
matches in two modern Sardinian populations, supporting a clear genealogical continuity from the Late Bronze Age up to current
times. The Nuragic populations appear to be part of a large and geographically unstructured cluster of modern European populations,
thus making it difficult to infer their evolutionary relationships. However, the low levels of genetic diversity, both within
and among ancient samples, as opposed to the sharp differences among modern Sardinian samples, support the hypothesis of the
expansion of a small group of maternally related individuals, and of comparatively recent differentiation of the Sardinian
gene pools.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
676.
Vallone D Frigato E Vernesi C Foà A Foulkes NS Bertolucci C 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,292(1):R160-R166
The molecular mechanisms whereby the circadian clock responds to temperature changes are poorly understood. The ruin lizard Podarcis sicula has historically proven to be a valuable vertebrate model for exploring the influence of temperature on circadian physiology. It is an ectotherm that naturally experiences an impressive range of temperatures during the course of the year. However, no tools have been available to dissect the molecular basis of the clock in this organism. Here, we report the cloning of three lizard clock gene homologs (Period2, Cryptochrome1, and Clock) that have a close phylogenetic relationship with avian clock genes. These genes are expressed in many tissues and show a rhythmic expression profile at 29 degrees C in light-dark and constant darkness lighting conditions, with phases comparable to their mammalian and avian counterparts. Interestingly, we show that at low temperatures (6 degrees C), cycling clock gene expression is attenuated in peripheral clocks with a characteristic increase in basal expression levels. We speculate that this represents a conserved vertebrate clock gene response to low temperatures. Furthermore, these results bring new insight into the issue of whether circadian clock function is compatible with hypothermia. 相似文献
677.
Alessandro Deplano Jessica Karlsson Federica Moraca Mona Svensson Claudia Cristiano Carmine Marco Morgillo Christopher J. Fowler Roberto Russo Bruno Catalanotti Valentina Onnis 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):940
Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1''-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds. 相似文献
678.
de Araujo Marcio José de Paula Rinaldo Cesar de Moraes Cristiano Bueno Pieroni Gustavo da Silva Paulo Henrique Müller 《Tree Genetics & Genomes》2021,17(5):1-16
Tree Genetics & Genomes - Malus baccata (L.) Borkh. and Malus toringo (Siebold) Siebold ex de Vriese of the genus Malus Mill. (Rosaceae) are wild crabapples occurring in temperate East Asia.... 相似文献
679.
Carla?J?Aguiar Jo?o?A?Rocha-Franco Pedro?A?Sousa Anderson?K?Santos Marina?Ladeira Cibele?Rocha-Resende Luiz?O?Ladeira Rodrigo?R?Resende Fernando?A?Botoni Marcos?Barrouin Melo Cristiano?X?Lima José?M?Carballido Thiago?M?Cunha Gustavo?B?Menezes Silvia?Guatimosim M?Fatima?LeiteEmail author 《Cell communication and signaling : CCS》2014,12(1):78
Background
Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models.Results
We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases.Conclusions
These results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.680.
Júlio Santos Maria Jo?o Gouveia Nuno Vale Maria de Lurdes Delgado Ana Gon?alves José M. Teixeira. da Silva Cristiano Oliveira Pedro Xavier Paula Gomes Lúcio L. Santos Carlos Lopes Alberto Barros Gabriel Rinaldi Paul J. Brindley José M. Correia da Costa Mário Sousa Mónica C. Botelho 《PloS one》2014,9(5)