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21.
Cláudia Marques Diana Teixeira Ana Cunha Manuela Meireles Diogo Pestana Elisa Keating Conceição Calhau Rosário Monteiro Ana Faria 《Cell biology and toxicology》2013,29(4):293-302
Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and 3H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 μM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. 3H-Deoxyglucose (3H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and 3H-thymidine incorporation (P?<?0.05). MTX (0.1 μM) treatment increased lipid accumulation and basal 3H-DG uptake by adipocytes (P?<?0.05). In 0.1 μM MTX-treated adipocytes, insulin stimulation did not result in an increase of 3H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX. 相似文献
22.
Lucas Cunha Dias de Rezende Fernando Fumagalli Marraiana Schiavon Bortolin Marianne Garcia de Oliveira Murilo Helder de Paula Valter Ferreira de Andrade-Neto Flavio da Silva Emery 《Bioorganic & medicinal chemistry letters》2013,23(16):4583-4586
1,4-Naphthoquinone derivatives are known to have relevant activities against several parasites. Among the treatment options for malaria, atovaquone, a 1,4-naphthoquinone derivative, is widely applied in the treatment and prophylaxis of such disease. Based on the structure simplification of atovaquone, we designed and synthesized four novel naphthoquinoidal derivatives. The compounds were obtained by the underexplored epoxide-opening reaction of 1,4-naphthoquinone using aniline derivatives as nucleophiles. The antiplasmodial activity of the synthesized compounds was performed in vivo using Peter’s 4 days suppression test. Significant parasitemia reduction and increased survival were observed for some of the compounds. 相似文献
23.
Sibelle Feitosa da Cunha Xavier Soares Andréia Aguiar Vieira Reinaldo Teixeira Delfino José Daniel Figueroa-Villar 《Bioorganic & medicinal chemistry》2013,21(18):5923-5930
Neurotoxic organophosphorus compounds (OPs), which are used as pesticides and chemical warfare agents lead to more than 700,000 intoxications worldwide every year. The main target of OPs is the inhibition of acetylcholinesterase (AChE), an enzyme necessary for the control of the neurotransmitter acetylcholine (ACh). The control of ACh function is performed by its hydrolysis with AChE, a process that can be completely interrupted by inhibition of the enzyme by phosphylation with OPs. Compounds used for reactivation of the phosphylated AChE are cationic oximes, which usually possess low membrane and hematoencephalic barrier permeation. Neutral oximes possess a better capacity for hematoencephalic barrier permeation.NMR spectroscopy is a very confident method for monitoring the inhibition and reactivation of enzymes, different from the Ellman test, which is the common method for evaluation of inhibition and reactivation of AChE. In this work 1H NMR was used to test the effect of neutral oximes on inhibition of AChE and reactivation of AChE inhibited with ethyl-paraoxon. The results confirmed that NMR is a very efficient method for monitoring the action of AChE, showing that neutral oximes, which display a significant AChE inhibition activity, are potential drugs for Alzheimer disease. The NMR method showed that a neutral oxime, previously indicated by the Ellman test as better in vitro reactivator of AChE inhibited with paraoxon than pralidoxime (2-PAM), was much less efficient than 2-PAM, confirming that NMR is a better method than the Ellman test. 相似文献
24.
Eliana Alves Maria A.F. Faustino João P.C. Tomé Maria G.P.M.S. Neves Augusto C. Tomé José A.S. Cavaleiro Ângela Cunha Newton C.M. Gomes Adelaide Almeida 《Bioorganic & medicinal chemistry》2013,21(14):4311-4318
Light activation of photosensitizing dyes in presence of molecular oxygen generates highly cytotoxic reactive oxygen species leading to cell inactivation. Nucleic acids are molecular targets of this photodynamic action but not considered the main cause of cell death. The in vivo effect of the photodynamic process on the intracellular nucleic acid content of Escherichia coli and Staphylococcus warneri was evaluated herein.Two cationic porphyrins (Tetra-Py+-Me and Tri-Py+-Me-PF) were used to photoinactivate E. coli (5.0 μM; 108 cells mL?1) and S. warneri (0.5 μM; 108 cells mL?1) upon white light irradiation at 4.0 mW cm?2 for 270 min and 40 min, respectively. Total nucleic acids were extracted from photosensitized bacteria after different times of irradiation and analyzed by agarose gel electrophoresis. The double-stranded DNA was quantified by fluorimetry and the porphyrin binding to bacteria was determined by spectrofluorimetry.E. coli was completely photoinactivated with both porphyrins (5.0 μM), whereas S. warneri was only completely inactivated by Tri-Py+-Me-PF (0.5 μM). The hierarchy of nucleic acid changes in E. coli was in the order: 23S rRNA > 16S rRNA > genomic DNA. The nucleic acids of S. warneri were extensively reduced after 5 min with Tri-Py+-Me-PF but almost unchanged with Tetra-Py+-Me after 40 min of irradiation. The amount of Tri-Py+-Me-PF bound to E. coli after washing the cells is higher than Tetra-Py+-Me and the opposite was observed for S. warneri. The binding capacity of the photosensitizers is not directly related to the PDI efficiency or nucleic acid reduction and this reduction occurs in parallel with the decrease of surviving cells. 相似文献
25.
M. E. Cunha P. Ré H. Quental‐Ferreira P. J. Gavaia P. Pousão‐Ferreira 《Journal of fish biology》2013,83(3):448-465
The larval development of the dusky grouper Epinephelus marginatus up to the benthic juvenile stage is described in detail to establish a reference for their larval identification. Development is described in terms of ontogenetic changes in morphology, growth, pigmentation, fin structure and skeletal structure. Larvae were reared in mesocosms at a mean temperature of 24·3° C, salinity of 36·5, dissolved oxygen of 6·4 mg l?1 and pH of 8·2. Newly hatched larvae had an estimated total length (LT) of 2·3 mm. On the second day post hatching the yolk was almost fully absorbed with traces of the oil globule still present, the eyes were already pigmented and mouth and gut functional. At this stage the cranial skeletal elements for feeding and breathing (mouth and gills) and the pectoral‐fin support were already present. About 50% of the observed larvae had food in their guts. Pigmentation was very characteristic, consisting of two large chromatophores visible on the edge of the primordial fin, close to the midpoint of the post‐anal region of the body and over the midgut and hindgut and post‐anal portion of the body. At 2·9 mm LT the emergence of the second dorsal‐fin spine, characteristic of the Epinephilinae, was clearly visible. The pre‐flexion stage started in larva of 3·2 mm LT. At 5·5 mm LT the larvae possessed posterior preopercular angle spines, and the dorsal and pelvic spines presented serrated edges and were pigmented. The water surface‐tension‐related death of the yolk sac and pre‐flexion larvae described in the rearing of several other grouper species did not occur during E. marginatus culture. Notochord flexion, with initial ossification of the caudal‐fin supporting elements, started at 6·6 mm LT. At this stage the major melanophores, preopercular, dorsal and pelvic spines and mandibular teeth were already present. Transformation of larvae into juveniles occurred when larvae averaged 13·8 mm LT. Juveniles with a mean LT of 20·1 mm started to settle and most of them were benthic with a mean LT of 26·8 mm. 相似文献
26.
Photosynthetic characteristics and quality of five passion fruit varieties under field conditions 总被引:1,自引:0,他引:1
Vinícius Novo Gama Joilton Tavares Cunha Inorbet de Melo Lima Marcos Antonio Bacarin Diolina Moura Silva 《Acta Physiologiae Plantarum》2013,35(3):941-948
Due to photosynthetic mechanisms respond very quickly to most stressors and due to strong concerns regarding the impact of climate change on future plant productivity, the purpose of this study was to perform a comparative analysis of in vivo photosynthetic efficiencies and fruit quality of five cultivars of passion fruit (Passiflora edulis Sims. f. flavicarpa Degener). The experiments were conducted in the northern region of Espírito Santo State using cultivars FB 200, FB 300, BRS Gigante Amarelo, BRS Sol do Cerrado, and BRS Ouro Vermelho. Analyses were performed 6 months after planting, when the plants were beginning reproduction and were repeated two times during the next 4 months until fruit ripening. Chlorophyll a fluorescence transient, total chlorophyll content, and gas exchange were measured in the leaves. Physical and chemical fruit attributes were also assessed. The lowest fluorescence rates were identified in the FB 300, BRS Sol do Cerrado, and BRS Ouro Vermelho cultivars, which exhibited better capacities for quinone A (QA) reoxidation and better electron transfer efficiencies from Photosystem II to Photosystem I acceptors. Better photochemical performances (PItotal) and CO2 assimilations (A) resulted in higher fruit pulp yields, demonstrating the superior quality of the FB 300, BRS Sol do Cerrado, and BRS Ouro Vermelho cultivars. 相似文献
27.
Tatiana Visnevschi-Necrasov Miguel A. Faria Sara C. Cunha J. Harris Harald W. E. Meimberg Manuel A. C. Curto M. Graça Pereira M. Beatriz P. P. Oliveira Eugénia Nunes 《Plant Systematics and Evolution》2013,299(2):357-367
This study presents the results of the identification and quantification of 12 isoflavones (prunetin, irilone, pseudobaptigenin, glycitein, daidzin, genistin, daidzein, pratensein, puerarin, biochanin A, formononetin and genistein) in 23 species of Trifolium (T. arvense, T. pratense, T. ligusticum, T. striatum, T. lappaceum, T. angustifolium, T. hirtum, T. subterraneum, T. isthmocarpum, T. stellatum, T. mutabile, T. strictum, T. fragiferum, T. alexandrinum, T. tomentosum. T. nigrescens subsp. petrisavii, T. nigrescens, T. glomeratum, T. subterraneum subsp. brachycalycinum, T. cherleri, T. resupinatum, T. campestre and T. repens). Isoflavones were extracted by an MSPD method and analyzed with HPLC coupled with a diode-array detector. The evaluation of molecular phylogeny of the IFS gene and the relation with isoflavone content was also performed. Five species (T. subterraneum subsp. brachycalycinum, T. alexandrinum, T. pratense, T. subterraneum and T. lappaceum) were identified with high levels of biochanin A (431–83 mg/kg), formononetin (72–365 mg/kg) and genistein (9–509 mg/kg), which could be utilized as alternative sources for the nutraceutical industry. Genetic phylogeny for the IFS gene was found in the species studied, with 20 out of 23 species having been divided into two clades, while the remaining three were genetically distant. Based on our results, we confirm the direct correlation between IFS gene polymorphism and isoflavones content in species of Trifolium particularly noted for formononetin. Therefore, the IFS gene can be utilized for screening Trifolium genotypes for formononetin. The relation of the three isoflavones' contents and the molecular phylogeny of plants determined by the IFS sequences, as a screening marker for plants with high isoflavone contents in Trifolium species, are to the best of our knowledge described for the first time. 相似文献
28.
Elaine F. F. da Cunha Edilaine F. Barbosa Aline A. Oliveira Teodorico C. Ramalho 《Journal of biomolecular structure & dynamics》2013,31(5):619-625
Abstract Mycobacterium tuberculosis (Mt) is a leading cause of infectious disease in the world today. This outlook is aggravated by a growing number of Mt infections in individuals who are immunocompromised as a result of HIV infections. Thus, new and more potent anti-tuberculosis agents are necessary. Therefore, DNA gyrase was selected as a target enzyme to combat Mt. In this work, the first three-dimensional molecular model of the hypothetical structures for the Mycobacterium tuberculosis DNA gyrase (mtDNAg) was elucidated by a homology modeling method. In addition, the orientations and binding affinities of some gatifloxacin analogs with those new structures were investigated. Our findings could be helpful for the design of new more potent gatifloxacin analogs. 相似文献
29.
Daniela Josa Elaine F.F. da Cunha Teodorico C. Ramalho Thais C.S. Souza Melissa S. Caetano 《Journal of biomolecular structure & dynamics》2013,31(4):373-376
Abstract Rifamicyns (Rifs) are antibiotic widely used for the treatment of tuberculosis (TB); nevertheless, their efficacy has been limited by a high percentage of mutations, principally in the rpoB gene. In this work, the first three-dimensional molecular model of the hypothetical structures for the wild-type and D516V and H526L mutants of Mycobacterium tuberculosis (mtRNAP) were elucidated by a homology modeling method. In addition, the orientations and binding affinities of some Rifs with those new structures were investigated. Our findings could be helpful for the design of new more potent rifamycin analogs. 相似文献
30.
For calculating the total annual Olea pollen concentration, the onset of the main pollen season and the peak pollen concentration dates, using data from 1998 to 2004, predictive models were developed using multiple regression analysis. Four Portuguese regions were studied: Reguengos de Monsaraz, Valença do Douro, Braga and Elvas. The effect of some meteorological parameters such as temperature and precipitation on Olea spatial and temporal airborne pollen distribution was studied. The best correlations were found when only the pre‐peak period was used, with thermal parameters (maximum temperature) showing the highest correlation with airborne pollen distribution. Independent variables, selected by regression analysis for the predictive models, with the greatest influence on the Olea main pollen season features were accumulated number of days with rain and rainfall in the previous autumn, and temperatures (average and minimum) from January through March. The models predict 59 to 99% of the total airborne pollen concentration recorded and the initial and peak concentration dates of the main Olea pollen season. 相似文献