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41.
J C Dorsman M A Smoor M L Maat-Schieman M Bout S Siesling S G van Duinen J J Verschuuren J T den Dunnen R A Roos G J van Ommen 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1999,354(1386):1061-1067
Huntington's disease (HD) is a neurodegenerative disorder with a midlife onset. The disease is caused by expansion of a CAG (glutamine) repeat within the coding region of the HD gene. The molecular mechanism by which the mutated protein causes this disease is still unclear. To study the protein we have generated a set of rabbit polyclonal antibodies raised against different segments of the N-terminal, central and C-terminal parts of the protein. The polyclonal antibodies were affinity purified and characterized in ELISA and Western blotting experiments. All antibodies can react with mouse and human proteins. The specificity of these antibodies is underscored by their recognition of huntingtin with different repeat sizes in extracts prepared from patient-derived lymphoblasts. The antibodies were used in immunofluorescence experiments to study the subcellular localization of huntingtin in mouse neuroblastoma NIE-115 cells. The results indicate that most huntingtin is present in the cytoplasm, whereas a minor fraction is present in the nucleus. On differentiation of the NIE-115 cells in vitro, the subcellular distribution of huntingtin does not change significantly. These results suggest that full-length huntingtin with a normal repeat length can be detected in the nucleus of cycling and non-cycling cultured mammalian cells of neuronal origin. However, in HD autopsy brain the huntingtin-containing neuronal intranuclear inclusions can be detected only with antibodies raised against the N-terminus of huntingtin. Thus several forms of huntingtin display the propensity for nuclear localization, possibly with different functional consequences. 相似文献
42.
Biobanking for Europe 总被引:1,自引:0,他引:1
Yuille M van Ommen GJ Bréchot C Cambon-Thomsen A Dagher G Landegren U Litton JE Pasterk M Peltonen L Taussig M Wichmann HE Zatloukal K 《Briefings in bioinformatics》2008,9(1):14-24
Biobanks are well-organized resources comprising biological samples and associated information that are accessible to scientific investigation. Across Europe, millions of samples with related data are held in different types of collections. While individual collections can be well organized and accessible, the resources are subject to fragmentation, insecurity of funding and incompleteness. To address these issues, a Biobanking and BioMolecular Resources Infrastructure (BBMRI) is to be developed across Europe, thereby implementing a European 'roadmap' for research infrastructures that was developed by a forum of EU member states and that has been received by the European Commission. In this review, we describe the work involved in preparing for the construction of BBMRI in a European and global context. 相似文献
43.
Wilfried Veron Nicole Orange Marc GJ Feuilloley Olivier Lesouhaitier 《BMC microbiology》2008,8(1):114
Background
Nervous tissues express various communication molecules including natriuretic peptides, i.e. Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP). These molecules share structural similarities with cyclic antibacterial peptides. CNP and to a lesser extent BNP can modify the cytotoxicity of the opportunistic pathogen Pseudomonas aeruginosa. The psychrotrophic environmental species Pseudomonas fluorescens also binds to and kills neurons and glial cells, cell types that both produce natriuretic peptides. In the present study, we investigated the sensitivity of Pseudomonas fluorescens to natriuretic peptides and evaluated the distribution and variability of putative natriuretic peptide-dependent sensor systems in the Pseudomonas genus. 相似文献44.
Gaelle Rossignol Annabelle Merieau Josette Guerillon Wilfried Veron Olivier Lesouhaitier Marc GJ Feuilloley Nicole Orange 《BMC microbiology》2008,8(1):189
Background
Pseudomonas fluorescens is a ubiquitous Gram-negative bacterium frequently encountered in hospitals as a contaminant of injectable material and surfaces. This psychrotrophic bacterium, commonly described as unable to grow at temperatures above 32°C, is now considered non pathogenic. We studied a recently identified clinical strain of P. fluorescens biovar I, MFN1032, which is considered to cause human lung infection and can grow at 37°C in laboratory conditions. 相似文献45.
Nutritional systems biology may be defined as the ultimate goal of molecular nutrition research, where all relevant aspects of regulation of metabolism in health and disease states at all levels of its complexity are taken into account to describe the molecular physiology of nutritional processes. The complexity spans from intracellular to inter-organ dynamics, and involves iterations between mathematical modelling and analysis employing all profiling methods and other biological read-outs. On the basis of such dynamic models we should be enabled to better understand how the nutritional status and nutritional challenges affect human metabolism and health. Although the achievement of this proposition may currently sound unrealistic, many initiatives in theoretical biology and biomedical sciences work on parts of the solution. This review provides examples and some recommendations for the molecular nutrition research arena to move onto the systems level. 相似文献
46.
Michela Baccini Eva-Maria Bachmaier Annibale Biggeri Mark V. Boekschoten Freek G. Bouwman Lorraine Brennan Robert Caesar Saverio Cinti Susan L. Coort Katie Crosley Hannelore Daniel Christian A. Drevon Susan Duthie Lars Eijssen Ruan M. Elliott Marjan van Erk Chris Evelo Mike Gibney Carolin Heim Graham W. Horgan Ian T. Johnson Thomas Kelder Robert Kleemann Teake Kooistra Martijn P. van Iersel Edwin C. Mariman Claus Mayer Gerard McLoughlin Michael Müller Francis Mulholland Ben van Ommen Abigael C. Polley Estelle Pujos-Guillot Isabel Rubio-Aliaga Helen M. Roche Baukje de Roos Manuela Sailer Giulia Tonini Lynda M. Williams Nicole de Wit 《Genes & nutrition》2008,3(3-4):147-151
47.
Human nutrition and metabolism may serve as the paradigm for the complex interplay of the genome with its environment. The concept of nutrigenomics now enables science with new tools and comprehensive analytical techniques to investigate this interaction at all levels of the complexity of the organism. Moreover, nutrigenomics seeks to better define the homeostatic control mechanisms, identify the de-regulation in the early phases of diet-related diseases, and attempts to assess to what extent an individual's sensitizing genotype contributes to the overall health or disease state. In a comparative approach nutrigenomics uses biological systems of increasing complexity from yeast to mammalian models to define the general rules of metabolic and genetic mechanisms in adaptations to the nutritional environment. Powerful information technology, bioinformatics and knowledge management tools as well as new mathematical and computational approaches now make it possible to study these molecular mechanisms at the cellular, organ and whole organism level and take it on to modeling the processes in a "systems biology" approach. This review summarizes some of the concepts of a comparative approach to nutrigenomics research, identifies current lacks and proposes a concerted scientific effort to create the basis for nutritional systems biology. 相似文献
48.
Dani?l B. van Schalkwijk Albert A. de Graaf Ben van Ommen Kees van Bochove Patrick C. N. Rensen Louis M. Havekes Niek C. A. van de Pas Huub C. J. Hoefsloot Jan van der Greef Andreas P. Freidig 《Journal of lipid research》2009,50(12):2398-2411
Increased plasma cholesterol is a known risk factor for cardiovascular disease. Lipoprotein particles transport both cholesterol and triglycerides through the blood. It is thought that the size distribution of these particles codetermines cardiovascular disease risk. New types of measurements can determine the concentration of many lipoprotein size-classes but exactly how each small class relates to disease risk is difficult to clear up. Because relating physiological process status to disease risk seems promising, we propose investigating how lipoprotein production, lipolysis, and uptake processes depend on particle size. To do this, we introduced a novel model framework (Particle Profiler) and evaluated its feasibility. The framework was tested using existing stable isotope flux data. The model framework implementation we present here reproduced the flux data and derived lipoprotein size pattern changes that corresponded to measured changes. It also sensitively indicated changes in lipoprotein metabolism between patient groups that are biologically plausible. Finally, the model was able to reproduce the cholesterol and triglyceride phenotype of known genetic diseases like familial hypercholesterolemia and familial hyperchylomicronemia. In the future, Particle Profiler can be applied for analyzing detailed lipoprotein size profile data and deriving rates of various lipolysis and uptake processes if an independent production estimate is given. 相似文献
49.
Mark Q Benedict Bart GJ Knols Hervé C Bossin Paul I Howell Eric Mialhe Carlos Caceres Alan S Robinson 《Malaria journal》2009,8(Z2):S4
Mosquitoes, just as other insects produced for the sterile insect technique (SIT), are subjected to several unnatural processes including laboratory colonisation and large-scale factory production. After these processes, sterile male mosquitoes must perform the natural task of locating and mating with wild females. Therefore, the colonisation and production processes must preserve characters necessary for these functions. Fortunately, in contrast to natural selection which favours a suite of characteristics that improve overall fitness, colonisation and production practices for SIT strive to maximize only the few qualities that are necessary to effectively control populations.However, there is considerable uncertainty about some of the appropriate characteristics due to the lack of data. Development of biological products for other applications suggest that it is possible to identify and modify competitiveness characteristics in order to produce competitive mass produced sterile mosquitoes. This goal has been pursued - and sometimes achieved - by mosquito colonisation, production, and studies that have linked these characteristics to field performance. Parallels are drawn to studies in other insect SIT programmes and aquaculture which serve as vital technical reference points for mass-production of mosquitoes, most of whose development occurs - and characteristics of which are determined - in an aquatic environment. Poorly understood areas that require further study are numerous: diet, mass handling and genetic and physiological factors that influence mating competitiveness. Compromises in such traits due to demands to increase numbers or reduce costs, should be carefully considered in light of the desired field performance. 相似文献
50.
Molecular chaperone proteins play a pivotal role in the protozoan parasite Leishmania donovani, controlling cell fate and ensuring intracellular survival. In higher eukaryotes, the so-called co-chaperone proteins are
required for client protein recognition and proper function of chaperones, among them the small glutamine-rich tetratricopeptide
repeat proteins (SGT) which interact with both HSP70 and HSP90 chaperones. An atypical SGT homolog is found in the L. donovani genome, encoding a protein lacking the C-terminal glutamine-rich region, normally typical for SGT family members. The gene
is expressed constitutively during the life cycle and is essential for survival and/or growth of the parasites. LdSGT forms
large, stable complexes that also include another putative co-chaperone, HSC70 interacting protein (HIP). The gene product
forms cytoplasmic clusters, matching the subcellular distribution of HIP and partly that of the major cytoplasmic chaperones,
HSP70 and HSP90, reflecting a direct molecular interaction with both chaperones. 相似文献