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991.
992.
Aviva Breuer Christeene G. Haj Manoela V. Foga?a Felipe V. Gomes Nicole Rodrigues Silva Jo?o Francisco Pedrazzi Elaine A. Del Bel Jaime C. Hallak José A. Crippa Antonio W. Zuardi Raphael Mechoulam Francisco S. Guimar?es 《PloS one》2016,11(7)
Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4''-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. 相似文献
993.
Bruno J. Neves Rodolpho C. Braga José C. B. Bezerra Pedro V. L. Cravo Carolina H. Andrade 《PLoS neglected tropical diseases》2015,9(1)
Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. 相似文献
994.
Aim To determine the relative contribution of species replacement and species richness differences to the emergence of beta‐diversity patterns. Innovation A novel method that disentangles all compositional differences (βcc, overall beta diversity) in its two components, species replacement (β‐3) and species richness differences (βrich) is proposed. The performance of the method was studied with ternary plots, which allow visualization of the influence of the relative proportions of shared and unique species of two sites over each metric. The method was also tested in different hypothetical gradients and with real datasets. The novel method was compared with a previous proposal based on the partitioning of overall compositional differences (βsor) in replacement (βsim) and nestedness (βnes). The linear response of βcc contrasts with the curvilinear response of βsor to linear gradients of dissimilarity. When two sites did not share any species, βsim was always 1 and β‐3 only reached 1 when the number of exclusive species of both sites was equal. β‐3 remained constant along gradients of richness differences with constant replacement, while βsim decreased. βrich had a linear response to a linear gradient of richness differences with constant species replacement, whereas βnes exhibited a hump‐shaped response. Moreover, βsim > βnes when clearly almost all species of one site were lost, whereas β‐3 < βrich in the same circumstances. Main conclusions The behaviour of the partition of βcc into β‐3 and βrich is consistent with the variation of replacement and richness differences. The partitioning of βsor into βsim and βnes overestimates the replacement component and underestimates richness differences. The novel methodology allows the discrimination of different causes of beta‐diversity patterns along latitudinal, biogeographic or ecological gradients, by estimating correctly the relative contributions of replacement and richness differences. 相似文献
995.
Alexandre Dobly Chloé Yzoard Christel Cochez Geneviève Ducoffre Marc Aerts Stefan Roels Paul Heyman 《Journal of vector ecology》2012,37(2):276-283
The transmission of pathogens to susceptible hosts is dependent on the vector population dynamics. In Europe, bank voles (Myodes glareolus) carry Puumala hantavirus, which causes nephropathia epidemica (NE) in humans. Fluctuations in bank vole populations and epidemics in humans are correlated but the main factors influencing this relationship remain unclear. In Belgium, more NE cases are reported in spring than in autumn. There is also a higher incidence of human infections during years of large vole populations. This study aimed to better understand the link between virus prevalence in the vector, vole demography, habitat quality, and human infections. Three rodent populations in different habitats bordering Brussels city, Belgium, were studied for two years. The seroprevalence in voles was influenced first by season (higher in spring), then by vole density, vole weight (a proxy for age), and capture site but not by year or sex. Moreover, voles with large maximal distance between two captures had a high probability for Puumala seropositivity. Additionally, the local vole density showed similar temporal variations as the number of NE cases in Belgium. These results showed that, while season was the main factor influencing vole seroprevalence, it was not sufficient to explain human risks. Indeed, vole density and weight, as well as the local habitat, were essential to understanding the interactions in these host‐pathogen dynamics. This can, in turn, be of importance for assessing the human risks. 相似文献
996.
Francisco S. Fernandes Francisco S. Ramalho José B. Malaquias Wesley A. C. Godoy Bárbara Davis B. Santos 《PloS one》2015,10(8)
Aphids cause significant damage to crop plants. Studies regarding predator-prey relationships in fennel (Foeniculum vulgare Mill.) and cotton (Gossypium hirsutum L.) crops are important for understanding essential ecological interactions in the context of intercropping and for establishing pest management programs for aphids. This study evaluated the association among Hyadaphis foeniculi (Passerini) (Hemiptera: Aphididae), Aphis gossypii Glover (Hemiptera: Aphididae) and Cycloneda sanguinea (L.) (Coleoptera: Coccinellidae) in cotton with coloured fibres, fennel and cotton intercropped with fennel. Association analysis was used to investigate whether the presence or absence of prey and predator species can indicate possible interactions between aphids and ladybugs. Significant associations among both apterous and alate H. foeniculi and C. sanguinea were observed in both the fennel and fennel-cotton intercropping systems. The similarity analysis showed that the presence of aphids and ladybugs in the same system is significantly dependent on the type of crop. A substantial amount of evidence indicates that the presence of the ladybug C. sanguinea, is associated with apterous or alate A. gossypii and H. foeniculi in fennel-cotton intercropping system. We recommend that future research vising integrated aphid management taking into account these associations for take decisions. 相似文献
997.
Sonia Tarazona Pedro Furió-Tarí David Turrà Antonio Di Pietro María José Nueda Alberto Ferrer Ana Conesa 《Nucleic acids research》2015,43(21):e140
As the use of RNA-seq has popularized, there is an increasing consciousness of the importance of experimental design, bias removal, accurate quantification and control of false positives for proper data analysis. We introduce the NOISeq R-package for quality control and analysis of count data. We show how the available diagnostic tools can be used to monitor quality issues, make pre-processing decisions and improve analysis. We demonstrate that the non-parametric NOISeqBIO efficiently controls false discoveries in experiments with biological replication and outperforms state-of-the-art methods. NOISeq is a comprehensive resource that meets current needs for robust data-aware analysis of RNA-seq differential expression. 相似文献
998.
Rita Casc?o Bruno Vidal Inês P. Lopes Eunice Paisana José Rino Luis F. Moita Jo?o E. Fonseca 《PloS one》2015,10(12)
Background
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).Methods
Celastrol was administered to AIA rats both in the early (4 days after disease induction) and late (11 days after disease induction) phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.Results
Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.Conclusions
Our results validate celastrol as a promising compound for the treatment of arthritis. 相似文献999.
1000.
Roberto Zenteno-Cuevas Francisco X Silva-Hernández Fabiola Mendoza-Damián Maria Dolores Ramírez-Hernández Karen Vázquez-Medina Lorena Widrobo-García Aremy Cuellar-Sanchez Raquel Mu?íz-Salazar Leonor Enciso-Moreno Lucia Monserrat Pérez-Navarro José Antonio Enciso-Moreno 《Memórias do Instituto Oswaldo Cruz》2013,108(6):718-723
Tuberculosis (TB) is an infectocontagious respiratory disease caused by members
of the Mycobacterium tuberculosis complex. A 7 base pair (bp)
deletion in the locus polyketide synthase
(pks)15/1 is described as polymorphic among members of the
M. tuberculosis complex, enabling the identification of
Euro-American, Indo-Oceanic and Asian lineages. The aim of this study was to
characterise this locus in TB isolates from Mexico. One hundred
twenty clinical isolates were recovered from the states of Veracruz and Estado
de Mexico. We determined the nucleotide sequence of a ± 400 bp fragment of the
locus pks15/1, while genotypic characterisation was
performed by spoligotyping. One hundred and fifty isolates contained the 7 bp
deletion, while five had the wild type locus. Lineages X (22%),
LAM (18%) and T (17%) were the most frequent; only three (2%) of the isolates
were identified as Beijing and two (1%) EAI-Manila. The wild type
pks15/1 locus was observed in all Asian lineage isolates
tested. Our results confirm the utility of locus pks15/1 as a
molecular marker for identifying Asian lineages of the M.
tuberculosis complex. This marker could be of great value in the
epidemiological surveillance of TB, especially in countries like Mexico, where
the prevalence of such lineages is unknown. 相似文献