全文获取类型
收费全文 | 4149篇 |
免费 | 310篇 |
国内免费 | 2篇 |
专业分类
4461篇 |
出版年
2023年 | 12篇 |
2022年 | 35篇 |
2021年 | 58篇 |
2020年 | 47篇 |
2019年 | 52篇 |
2018年 | 53篇 |
2017年 | 74篇 |
2016年 | 92篇 |
2015年 | 188篇 |
2014年 | 185篇 |
2013年 | 259篇 |
2012年 | 334篇 |
2011年 | 356篇 |
2010年 | 226篇 |
2009年 | 207篇 |
2008年 | 301篇 |
2007年 | 242篇 |
2006年 | 252篇 |
2005年 | 236篇 |
2004年 | 229篇 |
2003年 | 239篇 |
2002年 | 207篇 |
2001年 | 50篇 |
2000年 | 36篇 |
1999年 | 53篇 |
1998年 | 52篇 |
1997年 | 36篇 |
1996年 | 45篇 |
1995年 | 42篇 |
1994年 | 31篇 |
1993年 | 20篇 |
1992年 | 36篇 |
1991年 | 13篇 |
1990年 | 20篇 |
1989年 | 16篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 7篇 |
1985年 | 15篇 |
1984年 | 13篇 |
1983年 | 13篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1971年 | 3篇 |
1915年 | 1篇 |
排序方式: 共有4461条查询结果,搜索用时 15 毫秒
131.
As part of our continuing research for anticancer compounds from the Walloon Region forest, EtOAc extract from Carpinus betulus leaves was phytochemically studied, leading to the bioguided isolation of pheophorbide a, which is responsible of anticancer properties of C. betulus young leaves. This compound was identified using nuclear magnetic resonance and mass spectrophotometric data and comparison with a commercial standard. Evaluation of the growth inhibitory activities of pheophorbide a using MTT colorimetric assay and phase-contrast microscopy in various human cancer cell lines confirmed the photoactivable properties of this compound. Our research showed, for the first time, the presence of pheophorbide a, a chlorophyll derived compound, which we quantified in high quantities in young leaves of C. betulus. This is in contrast with the literature which generally describes pheophorbide a as a catabolic product of chlorophyll, then preferentially present in old leaves. 相似文献
132.
Valeria Agamennone Joeri van Straalen Abraham Brouwer Tjalf E. de Boer Paul J. Hensbergen Niels Zaagman Martin Braster Nico M. van Straalen Dick Roelofs Thierry K.S. Janssens 《Entomologia Experimentalis et Applicata》2019,167(3):269-285
Antibiotic resistance necessitates the search for new bioactive compounds with novel mechanisms of action. Natural products derived from bacteria and fungi are widely used in the field of medicine and new environments can be explored as sources of antimicrobials. Bacteria associated with springtails have shown high inhibitory activity against pathogens. Here, we characterized a bacterial strain with high potential for antimicrobial activity, isolated from the gut of the springtail Folsomia candida Willem (Collembola: Isotomidae). The strain was characterized using the ‘analytical profile index’ and the ‘minimal inhibitory concentration’ assay to test for antibiotic resistance. Agar overlay and agar disk diffusion assays were used to test the inhibitory activity of the strain and its extract against a variety of pathogens, and reporter assays were used to investigate the mode of action. High‐performance liquid chromatography was used to analyze and fractionate the extract of bacterial culture, followed by additional assays on the fractions. The genome of the strain was screened for presence of antibiotic resistance genes and secondary metabolite gene clusters. The isolate was identified as Bacillus toyonensis Jiménez et al., but it displayed differences in metabolic profile when compared to the type species. The isolate was highly resistant to penicillin and inhibited the growth of a variety of pathogenic microorganisms. Genome analysis revealed an enrichment of resistance genes for β‐lactam antibiotics compared to the type isolate. Also, secondary metabolite clusters involved in the production of siderophores, bacteriocins, and nonribosomal peptide synthetases were identified. In conclusion, a unique Bacillus strain was isolated from the gut of F. candida, for which we provide evidence of inhibitory activity against an array of pathogens. This, coupled with high resistance to penicillin as substantiated by the presence of resistance genes, points to the potential of B. toyonensis VU‐DES13 to provide a new source of antimicrobial compounds. 相似文献
133.
Roselyne Ferrari Isabelle Lacaze Pauline Le Faouder Justine Bertrand-Michel Camille Oger Jean-Marie Galano Thierry Durand Stéphane Moularat Laetitia Chan Ho Tong Charlie Boucher Jaafar Kilani Yohann Petit Océane Vanparis César Trannoy Sylvain Brun Hervé Lalucque Fabienne Malagnac Philippe Silar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2174-2182
Oxylipins are secondary messengers used universally in the living world for communication and defense. The paradigm is that they are produced enzymatically for the eicosanoids and non-enzymatically for the isoprostanoids. They are supposed to be degraded into volatile organic compounds (VOCs) and to participate in aroma production. Some such chemicals composed of eight carbons are also envisoned as alternatives to fossil fuels. In fungi, oxylipins have been mostly studied in Aspergilli and shown to be involved in signalling asexual versus sexual development, mycotoxin production and interaction with the host for pathogenic species. Through targeted gene deletions of genes encoding oxylipin-producing enzymes and chemical analysis of oxylipins and volatile organic compounds, we show that in the distantly-related ascomycete Podospora anserina, isoprostanoids are likely produced enzymatically. We show the disappearance in the mutants lacking lipoxygenases and cyclooxygenases of the production of 10-hydroxy-octadecadienoic acid and that of 1-octen-3-ol, a common volatile compound. Importantly, this was correlated with the inability of the mutants to repel nematodes as efficiently as the wild type. Overall, our data show that in this fungus, oxylipins are not involved in signalling development but may rather be used directly or as precursors in the production of odors against potential agressors.
Significance
We analyzse the role in inter-kingdom communication of lipoxygenase (lox) and cyclooxygenase (cox) genes in the model fungus Podospora anserina.Through chemical analysis we define the oxylipins and volatile organic compounds (VOCs)produce by wild type and mutants for cox and lox genes,We show that the COX and LOX genes are required for the production of some eight carbon VOCs.We show that COX and LOX genes are involved in the production of chemicals repelling nematodes.This role is very different from the ones previously evidenced in other fungi. 相似文献134.
Bihag Anothumakkool Simon Wiemers‐Meyer Dominique Guyomard Martin Winter Thierry Brousse Joel Gaubicher 《Liver Transplantation》2019,9(27)
An industry‐relevant method for pre‐lithiation of lithium‐ion capacitors to balance the first charge irreversibility is demonstrated, which addresses the prime bottleneck for their market integration. Based on a composite positive electrode that integrates pyrene monomers and an insoluble lithiated base, Li3PO4, a “cascade‐type” process involving two consecutive irreversible reactions is proposed: i) oxidative electropolymerization of the pyrene moieties releases electrons and protons; ii) protons are captured by Li3PO4 and exchanged for a stoichiometric amount of Li+ into the electrolyte. (1H, 19F, and 31P) NMR spectroscopy, operando X‐ray diffraction, and Raman spectroscopy support this mechanism. By decoupling the irreversible source of lithium ions from electrons, the cascade‐type pre‐lithiation allows the simultaneous enhancement of the capacity of the positive electrode, thanks to p‐doping of the resulting polymer. Remarkably, the proton scavenging properties of Li3PO4 also boost the polymerization process, which enables a 16% increase in capacity without detrimental effect on power properties and cyclability. Full cells integrating a cheap carbon black based negative electrode, show much‐improved capacity of 17 mAh g‐1electrodes (44 F g‐1electrodes, 3–4.4 V) and excellent stability over 2200 cycles at 1 A g‐1. Thanks to its versatile chemistry and flexibility this approach in principle can be applied to any kind of ion‐battery. 相似文献
135.
Thierry Chambert David S. Pilliod Caren S. Goldberg Hideyuki Doi Teruhiko Takahara 《Ecology and evolution》2018,8(6):3468-3477
Environmental DNA (eDNA) analysis of water samples is on the brink of becoming a standard monitoring method for aquatic species. This method has improved detection rates over conventional survey methods and thus has demonstrated effectiveness for estimation of site occupancy and species distribution. The frontier of eDNA applications, however, is to infer species density. Building upon previous studies, we present and assess a modeling approach that aims at inferring animal density from eDNA. The modeling combines eDNA and animal count data from a subset of sites to estimate species density (and associated uncertainties) at other sites where only eDNA data are available. As a proof of concept, we first perform a cross‐validation study using experimental data on carp in mesocosms. In these data, fish densities are known without error, which allows us to test the performance of the method with known data. We then evaluate the model using field data from a study on a stream salamander species to assess the potential of this method to work in natural settings, where density can never be known with absolute certainty. Two alternative distributions (Normal and Negative Binomial) to model variability in eDNA concentration data are assessed. Assessment based on the proof of concept data (carp) revealed that the Negative Binomial model provided much more accurate estimates than the model based on a Normal distribution, likely because eDNA data tend to be overdispersed. Greater imprecision was found when we applied the method to the field data, but the Negative Binomial model still provided useful density estimates. We call for further model development in this direction, as well as further research targeted at sampling design optimization. It will be important to assess these approaches on a broad range of study systems. 相似文献
136.
Asen Daskalov Matthias Gantner Marielle Aulikki W?lti Thierry Schmidlin Celestine N. Chi Christian Wasmer Anne Schütz Johanna Ceschin Corinne Clavé Sandra Cescau Beat Meier Roland Riek Sven J. Saupe 《PLoS pathogens》2014,10(6)
The [Het-s] prion of the fungus Podospora anserina represents a good model system for studying the structure-function relationship in amyloid proteins because a high resolution solid-state NMR structure of the amyloid prion form of the HET-s prion forming domain (PFD) is available. The HET-s PFD adopts a specific β-solenoid fold with two rungs of β-strands delimiting a triangular hydrophobic core. A C-terminal loop folds back onto the rigid core region and forms a more dynamic semi-hydrophobic pocket extending the hydrophobic core. Herein, an alanine scanning mutagenesis of the HET-s PFD was conducted. Different structural elements identified in the prion fold such as the triangular hydrophobic core, the salt bridges, the asparagines ladders and the C-terminal loop were altered and the effect of these mutations on prion function, fibril structure and stability was assayed. Prion activity and structure were found to be very robust; only a few key mutations were able to corrupt structure and function. While some mutations strongly destabilize the fold, many substitutions in fact increase stability of the fold. This increase in structural stability did not influence prion formation propensity in vivo. However, if an Ala replacement did alter the structure of the core or did influence the shape of the denaturation curve, the corresponding variant showed a decreased prion efficacy. It is also the finding that in addition to the structural elements of the rigid core region, the aromatic residues in the C-terminal semi-hydrophobic pocket are critical for prion propagation. Mutations in the latter region either positively or negatively affected prion formation. We thus identify a region that modulates prion formation although it is not part of the rigid cross-β core, an observation that might be relevant to other amyloid models. 相似文献
137.
Mehdy Ratajczak Emilie Laroche Thierry Berthe Olivier Clermont Barbara Pawlak Erick Denamur Fabienne Petit 《BMC microbiology》2010,10(1):222
Background
Escherichia coli is a commensal bacterium of the gastro-intestinal tract of human and vertebrate animals, although the aquatic environment could be a secondary habitat. The aim of this study was to investigate the effect of hydrological conditions on the structure of the E. coli population in the water of a creek on a small rural watershed in France composed of pasture and with human occupation. 相似文献138.
Julier B Huguet T Chardon F Ayadi R Pierre JB Prosperi JM Barre P Huyghe C 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2007,114(8):1391-1406
In many legume crops, especially in forage legumes, aerial morphogenesis defined as growth and development of plant organs,
is an essential trait as it determines plant and seed biomass as well as forage quality (protein concentration, dry matter
digestibility). Medicago truncatula is a model species for legume crops. A set of 29 accessions of M. truncatula was evaluated for aerial morphogenetic traits. A recombinant inbred lines (RILs) mapping population was used for analysing
quantitative variation in aerial morphogenetic traits and QTL detection. Genes described to be involved in aerial morphogenetic
traits in other species were mapped to analyse co-location between QTLs and genes. A large variation was found for flowering
date, morphology and dynamics of branch elongation among the 29 accessions and within the RILs population. Flowering date
was negatively correlated to main stem and branch length. QTLs were detected for all traits, and each QTL explained from 5.2
to 59.2% of the phenotypic variation. A QTL explaining a large part of genetic variation for flowering date and branch growth
was found on chromosome 7. The other chromosomes were also involved in the variation detected in several traits. Mapping of
candidate genes indicates a co-location between a homologue of Constans gene or a flowering locus T (FT) gene and the QTL
of flowering date on chromosome 7. Other candidate genes for several QTLs are described.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
139.
Virginie Rougeron Thierry De Mee?s Sandrine Kako Ouraga Mallorie Hide Anne-Laure Ba?uls 《PLoS pathogens》2010,6(8)
Leishmaniases remain a major public health problem today (350 million people at risk, 12 million infected, and 2 million new infections per year). Despite the considerable progress in cellular and molecular biology and in evolutionary genetics since 1990, the debate on the population structure and reproductive mode of Leishmania is far from being settled and therefore deserves further investigation. Two major hypotheses coexist: clonality versus sexuality. However, because of the lack of clear evidence (experimental or biological confirmation) of sexuality in Leishmania parasites, until today it has been suggested and even accepted that Leishmania species were mainly clonal with infrequent genetic recombination (see [1] for review). Two recent publications, one on Leishmania major (an in vitro experimental study) and one on Leishmania braziliensis (a population genetics analysis), once again have challenged the hypothesis of clonal reproduction. Indeed, the first study experimentally evidenced genetic recombination and proposed that Leishmania parasites are capable of having a sexual cycle consistent with meiotic processes inside the insect vector. The second investigation, based on population genetics studies, showed strong homozygosities, an observation that is incompatible with a predominantly clonal mode of reproduction at an ecological time scale (∼20–500 generations). These studies highlight the need to advance the knowledge of Leishmania biology. In this paper, we first review the reasons stimulating the continued debate and then detail the next essential steps to be taken to clarify the Leishmania reproduction model. Finally, we widen the discussion to other Trypanosomatidae and show that the progress in Leishmania biology can improve our knowledge of the evolutionary genetics of American and African trypanosomes. 相似文献
140.