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11.
Alice B.M. Lanne Alice Goode Charlotte Prattley Divya Kumari Mette Ryun Drasbek Paul Williams Raquel Conde-Álvarez Ignacio Moriyón Boyan B. Bonev 《生物化学与生物物理学报:生物膜》2019,1861(1):83-92
Nisin is a lanthionine antimicrobial effective against diverse Gram-positive bacteria and is used as a food preservative worldwide. Its action is mediated by pyrophosphate recognition of the bacterial cell wall receptors lipid II and undecaprenyl pyrophosphate. Nisin/receptor complexes disrupt cytoplasmic membranes, inhibit cell wall synthesis and dysregulate bacterial cell division. Gram-negative bacteria are much more tolerant to antimicrobials including nisin. In contrast to Gram-positives, Gram-negative bacteria possess an outer membrane, the major constituent of which is lipopolysaccharide (LPS). This contains surface exposed phosphate and pyrophosphate groups and hence can be targeted by nisin. Here we describe the impact of LPS on membrane stability in response to nisin and the molecular interactions occurring between nisin and membrane-embedded LPS from different Gram-negative bacteria. Dye release from liposomes shows enhanced susceptibility to nisin in the presence of LPS, particularly rough LPS chemotypes that lack an O-antigen whereas LPS from microorganisms sharing similar ecological niches with antimicrobial producers provides only modest enhancement. Increased susceptibility was observed with LPS from pathogenic Klebsiella pneumoniae compared to LPS from enteropathogenic Salmonella enterica and gut commensal Escherichia coli. LPS from Brucella melitensis, an intra-cellular pathogen which is adapted to invade professional and non-professional phagocytes, appears to be refractory to nisin. Molecular complex formation between nisin and LPS was studied by solid state MAS NMR and revealed complex formation between nisin and LPS from most organisms investigated except B. melitensis. LPS/nisin complex formation was confirmed in outer membrane extracts from E. coli. 相似文献
12.
Gloria Alvarez-Sola Iker Uriarte Maria U. Latasa Maddalen Jimenez Marina Barcena-Varela Eva Santamaría Raquel Urtasun Carlos Rodriguez-Ortigosa Jesús Prieto Pedro Berraondo Maite G. Fernandez-Barrena Carmen Berasain Matías A. Avila 《生物化学与生物物理学报:疾病的分子基础》2018,1864(4):1326-1334
The liver has an extraordinary regenerative capacity rapidly triggered upon injury or resection. This response is intrinsically adjusted in its initiation and termination, a property termed the “hepatostat”. Several molecules have been involved in liver regeneration, and among them bile acids may play a central role. Intrahepatic levels of bile acids rapidly increase after resection. Through the activation of farnesoid X receptor (FXR), bile acids regulate their hepatic metabolism and also promote hepatocellular proliferation. FXR is also expressed in enterocytes, where bile acids stimulate the expression of fibroblast growth factor 15/19 (FGF15/19), which is released to the portal blood. Through the activation of FGFR4 on hepatocytes FGF15/19 regulates bile acids synthesis and finely tunes liver regeneration as part of the “hepatostat”. Here we review the experimental evidences supporting the relevance of the FXR-FGF15/19-FGFR4 axis in liver regeneration and discuss potential therapeutic applications of FGF15/19 in the prevention of liver failure. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen. 相似文献
13.
Robo4 maintains vessel integrity and inhibits angiogenesis by interacting with UNC5B 总被引:1,自引:0,他引:1
Koch AW Mathivet T Larrivée B Tong RK Kowalski J Pibouin-Fragner L Bouvrée K Stawicki S Nicholes K Rathore N Scales SJ Luis E del Toro R Freitas C Bréant C Michaud A Corvol P Thomas JL Wu Y Peale F Watts RJ Tessier-Lavigne M Bagri A Eichmann A 《Developmental cell》2011,20(1):33-46
Robo4 is an endothelial cell-specific member of the Roundabout axon guidance receptor family. To identify Robo4 binding partners, we performed a protein-protein interaction screen with the Robo4 extracellular domain. We find that Robo4 specifically binds to UNC5B, a vascular Netrin receptor, revealing unexpected interactions between two endothelial guidance receptors. We show that Robo4 maintains vessel integrity by activating UNC5B, which inhibits signaling downstream of vascular endothelial growth factor (VEGF). Function-blocking monoclonal antibodies against Robo4 and UNC5B increase angiogenesis and disrupt vessel integrity. Soluble Robo4 protein inhibits VEGF-induced vessel permeability and rescues barrier defects in Robo4(-/-) mice, but not in mice treated with anti-UNC5B. Thus, Robo4-UNC5B signaling maintains vascular integrity by counteracting VEGF signaling in endothelial cells, identifying a novel function of guidance receptor interactions in the vasculature. 相似文献
14.
P-glycoprotein has a widespread expression on normal tissues. The protein has also been strongly associated with the multidrug resistance phenotype (MDR) on tumor cells. The employment of flow cytometry and confocal microscopy has contributed to the discovery and application of new particular fluorescent dyes. Nevertheless, several studies are being performed in different cellular types neglecting the expression/activity of MDR proteins. Because many fluorochromes have been reported as P-glycoprotein substrates, an especial attention must be given to the properties of new dyes in the presence of MDR proteins. Flow cytometric analyzes of Mitotracker Green (MTG) fluorescence profile were performed in a human erythroleukemic cell line and its resistant counterpart. In this report we demonstrated that MTG, a probe used to evaluate the mitochondrial mass, is a P-glycoprotein substrate and its staining profile is dependent on the activity of this protein. In vitro studies on a human erythroleukemic cell line and its resistant counterpart revealed that MDR modulators (Cyclosporin A, Verapamil, and Trifluoperazine) alter the MTG fluorescence pattern on a resistant cell line. The findings suggest that attention should be given to the expression of P-glycoprotein when performing an evaluation of mitochondria properties with MTG. 相似文献
15.
16.
Pedro Almeida Raquel Barbosa Polona Zalar Yumi Imanishi Kiminori Shimizu Benedetta Turchetti Jean‐Luc Legras Marta Serra Sylvie Dequin Arnaud Couloux Julie Guy Douda Bensasson Paula Gonçalves José Paulo Sampaio 《Molecular ecology》2015,24(21):5412-5427
The domestication of the wine yeast Saccharomyces cerevisiae is thought to be contemporary with the development and expansion of viticulture along the Mediterranean basin. Until now, the unavailability of wild lineages prevented the identification of the closest wild relatives of wine yeasts. Here, we enlarge the collection of natural lineages and employ whole‐genome data of oak‐associated wild isolates to study a balanced number of anthropic and natural S. cerevisiae strains. We identified industrial variants and new geographically delimited populations, including a novel Mediterranean oak population. This population is the closest relative of the wine lineage as shown by a weak population structure and further supported by genomewide population analyses. A coalescent model considering partial isolation with asymmetrical migration, mostly from the wild group into the Wine group, and population growth, was found to be best supported by the data. Importantly, divergence time estimates between the two populations agree with historical evidence for winemaking. We show that three horizontally transmitted regions, previously described to contain genes relevant to wine fermentation, are present in the Wine group but not in the Mediterranean oak group. This represents a major discontinuity between the two populations and is likely to denote a domestication fingerprint in wine yeasts. Taken together, these results indicate that Mediterranean oaks harbour the wild genetic stock of domesticated wine yeasts. 相似文献
17.
Raquel Lopez-Pardo Jose Ignacio Ruiz de Galarreta Enrique Ritter 《Molecular breeding : new strategies in plant improvement》2013,31(1):39-45
Quantitative real-time polymerase chain reaction (qRT-PCR) is currently the most sensitive method used for quantitative gene expression studies. However, minimal variation in the amount of material and presence of inhibitors affecting enzyme efficiency can lead to significant quantification errors. Accurate data normalization is vital using reference genes as internal controls. Many so-called housekeeping genes or reference genes with assumed stable expression can exhibit either up- or downregulation depending on the developmental stage or other environmental conditions. We have evaluated six reference genes (actin, APRT, 18S rRNA, ef1α, β-tubulin and ribosomal protein L2) for qRT-PCR profiling experiments in potato tuber tissues of five varieties during cold storage at different temperatures and treatment periods. Genes were ranked according to their expression stability by BestKeeper, geNorm and NormFinder software tools in the same order. This means that any of them can be used for this purpose. The results indicated that ef1α and APRT were the most stably expressed genes in the potato tuber tissues under different cold storage regimes. We therefore recommend use of this pair of genes as internal controls for gene expression studies under the described conditions. 相似文献
18.
We measured the production of untargeted mutations in the cI and cII genes of untreated λ phage undergoing a lytic cycle in UV-irradiated bacterial hosts. As previously shown, treatment with 4 μg/ml of rifampicin during post-irradiation incubation inhibited amplification of the RecA protein in these cells. In addition, we observed a decreased mutation rate compared to the untreated, irradiated bacteria. Treatment with 4 μg/ml or 8 μg/ml rifampicin did not prevent the UV induction of the umuDC operon, as judged by assay of β-galactosidase activity in a umuC-lacZ fusion strain. In contrast, the UV-induction of β-galactosidase in the sulA-lacZ fusion strain was decreased by 4 μg/ml rifampicin. The inhibition of untargeted mutagenesis by this drug treatment was also observed in a strain constitutive for SOS functions (lexA (Def)) as well as ina RecA-overproducing plasmid strain, that blocks induction of heat-shock proteins, factor(s) in wild-type recA+ cells. An htpR165-carrying strain, that blocks induction of heat-shock proteins, exhibited normal UV-promoted mutagenesis. A correlation was observed between the cellular concentration of RecA protein, increased spontaneously by a temperature shift in a lexA(Ts) strain, and the extent of UV-promoted untargeted mutagenesis. These results suggest a mechanistic role of RecA protein in this process. 相似文献
19.
Stefanie Wagner Frédéric Lagane Andaine Seguin‐Orlando Mikkel Schubert Thibault Leroy Erwan Guichoux Emilie Chancerel Inger Bech‐Hebelstrup Vincent Bernard Cyrille Billard Yves Billaud Matthias Bolliger Christophe Croutsch Katarina Čufar Frédérique Eynaud Karl Uwe Heussner Joachim Köninger Fabien Langenegger Frédéric Leroy Christine Lima Nicoletta Martinelli Garry Momber André Billamboz Oliver Nelle Antoni Palomo Raquel Piqué Marianne Ramstein Roswitha Schweichel Harald Stäuble Willy Tegel Xavier Terradas Florence Verdin Christophe Plomion Antoine Kremer Ludovic Orlando 《Molecular ecology》2018,27(5):1138-1154
Reconstructing the colonization and demographic dynamics that gave rise to extant forests is essential to forecasts of forest responses to environmental changes. Classical approaches to map how population of trees changed through space and time largely rely on pollen distribution patterns, with only a limited number of studies exploiting DNA molecules preserved in wooden tree archaeological and subfossil remains. Here, we advance such analyses by applying high‐throughput (HTS) DNA sequencing to wood archaeological and subfossil material for the first time, using a comprehensive sample of 167 European white oak waterlogged remains spanning a large temporal (from 550 to 9,800 years) and geographical range across Europe. The successful characterization of the endogenous DNA and exogenous microbial DNA of 140 (~83%) samples helped the identification of environmental conditions favouring long‐term DNA preservation in wood remains, and started to unveil the first trends in the DNA decay process in wood material. Additionally, the maternally inherited chloroplast haplotypes of 21 samples from three periods of forest human‐induced use (Neolithic, Bronze Age and Middle Ages) were found to be consistent with those of modern populations growing in the same geographic areas. Our work paves the way for further studies aiming at using ancient DNA preserved in wood to reconstruct the micro‐evolutionary response of trees to climate change and human forest management. 相似文献