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1.
Speciation with gene flow is greatly facilitated when traits subject to divergent selection also contribute to non-random mating. Such traits have been called 'magic traits', which could be interpreted to imply that they are rare, special, or unrealistic. Here, we question this assumption by illustrating that magic traits can be produced by a variety of mechanisms, including ones in which reproductive isolation arises as an automatic by-product of adaptive divergence. We also draw upon the theoretical literature to explore whether magic traits have a unique role in speciation or can be mimicked in their effects by physically linked trait-complexes. We conclude that magic traits are more frequent than previously perceived, but further work is needed to clarify their importance.  相似文献   
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Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.  相似文献   
3.
    
As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg−/− mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg−/− mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.  相似文献   
4.
Liposomes have become popular drug delivery vehicles and have more recently also been applied as contrast agents for molecular imaging. Most current methods for functionalization of liposomes with targeting proteins rely on reactions of amine or thiol groups at the protein exterior, which generally result in nonspecific conjugation at multiple sites on the protein. In this study, we present native chemical ligation (NCL) as a general method to covalently couple recombinant proteins in a highly specific and chemoselective way to liposomes containing cysteine-functionalized phospholipids. A cysteine-functionalized phospholipid (Cys-PEG-DSPE) was prepared and shown to readily react with the MESNA thioester of EYFP, which was used as a model protein. Characterization of the EYFP-liposomes using fluorescence spectroscopy showed full retention of the fluorescent properties of conjugated EYFP and provides a lower limit of 120 proteins per liposome. The general applicability of NCL was further tested using CNA35, a collagen-binding protein recently applied in fluorescent imaging of collagen. NCL of CNA35 thioester yielded liposomes containing approximately 100 copies of CNA35 per liposome. The CNA35-liposomes were shown to be fully functional and bind collagen with a 150-fold higher affinity compared to CNA35. Our results show that NCL is an attractive addition to existing conjugation methods that allows direct, covalent, and highly specific coupling of recombinant proteins to liposomes and other lipid-based assemblies.  相似文献   
5.
Houten SM  Argmann CA 《Cell》2011,147(4):719-721
Cholesterol regulates activation of sterol regulatory element-binding protein (SREBP) through a classic feedback loop. Walker et al. (2011) extend the regulatory inputs governing SREBP activity to include an independent loop modulated by phosphatidylcholine (PC) and cellular methylation capacity. These findings suggest a link between lipid synthesis and cellular pathways involved in methylation.  相似文献   
6.
The aim of this review is to present a concise overview of all data available on the immunogenetics of Chlamydia trachomatis infections, both sexually transmitted urogenital and ocular infections. Currently, candidate gene approaches are used to identify genes related to the susceptibility to and severity of C. trachomatis infections. The main focus in the review will be on data obtained by the study of human cohorts.  相似文献   
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8.
2-Iodo-3-ureidopropionic acid resulting from the hydrolysis of 5-iodo-5,6-dihydrouracil catalyzed by either dihydrouracil amidohydrolase or hydroxide ion cyclizizes to yield 2-amino-2-oxazoline-3-carboxylic acid. This cyclization involves intramolecular attack of the ureido oxygen atom on carbon two of the ureidoacid to yield iodide ion and the oxazoline as products. The kinetics of this cyclization indicate that from pH 2 to 9 the reaction rate is pH independent. Below pH 2 the rate is diminished due to protonation of the ureido group. Above pH 12 the rate increases dramatically probably due to proton abstraction which would dramatically increase the nucleophilic character of the ureido function. In the pH independent region the reaction is not subject to catalysis by external buffers.  相似文献   
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10.
European landscapes have been shaped over the centuries by processes related to human land use, which are reflected in regionally distinct landscape patterns. Since landscape pattern has been linked to biodiversity and other ecological values of the landscapes, this paper explores landscape pattern as a tool for ecological sustainability assessments at the regional (Austrian Cultural Landscapes), national (Austria) and European (European Union + Norway, Switzerland) level with focus on agricultural landscapes. A set of landscape metrics served as a basis to assess naturalness and geometrisation of Austrian and European landscapes as a proxy for their sustainability. To achieve an accurate spatially explicit assessment, we applied a spatial reference framework consisting in units that are homogeneous in biophysical and socio-economic contexts, adapted the regional approach for its application at European level, and developed relative sustainability thresholds for the landscape metrics. The analyses revealed that several landscape metrics, particularly the “Number of Shape Characterising Points” showed a high correlation with the degree of naturalness. The sustainability map of Austria based on an ordinal regression model revealed well-known problem regions of ecological sustainability. At the European level, the relative deviation from the average pattern showed clearly the simplification processes in the landscapes. However, a better spatial resolution of land cover data would add to the refinement of pattern analysis in regions and therefore the assessment of sustainability. We recommend the combination of information of different scales for the formulation and implementation of sustainability policies.  相似文献   
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