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121.
F. C. Connell P. Ostergaard C. Carver G. Brice N. Williams S. Mansour P. S. Mortimer Steve Jeffery Lymphoedema Consortium 《Human genetics》2009,124(6):625-631
Milroy disease (hereditary lymphoedema type I, MIM 153100) is a congenital onset primary lymphoedema with autosomal dominant
inheritance. Mutations in the gene, vascular endothelial growth factor receptor 3, VEGFR3 (FLT4), are known to cause Milroy disease, but there is uncertainty about the prevalence of VEGFR3 mutations in patients with primary lymphoedema and more specifically in those with a phenotype that resembles Milroy disease.
This study aims to address this issue and thereby delineate the Milroy disease phenotype. Fifty-two patients with primary
lymphoedema were analysed for mutations in the coding regions of VEGFR3. Patients were divided into four groups: Typical Milroy disease with family history (group I), typical Milroy disease with
no family history (group II), atypical Milroy disease (group III), and complex primary lymphoedema (group IV). Results demonstrated
that with rigorous phenotyping the likelihood of detecting VEGFR3 mutations is optimised. Mutation prevalence is 75% in typical Milroy patients with a family history (group I) and 68% if
positive family history is not a diagnostic criterion. A positive family history is not essential in Milroy disease. The likelihood
of detecting VEGFR3 mutations in patients who have a phenotype which is not typical of Milroy disease is very small (<5%). For the 22 mutation
positive patients, 14 novel VEGFR3 mutations were identified, two of which were in exon 22 and one in exon 17, confirming that these exons should be included
in VEGFR3 analysis. No mutations were found outside the kinase domains, showing that analysis of this part of the gene is not useful
for Milroy disease patients. VEGFC, which encodes the ligand for VEGFR3, was sequenced in all patients with typical Milroy disease (groups I and II) and no
mutations were identified.
F. C. Connell and P. Ostergaard contributed equally to this work.
An erratum to this article can be found at 相似文献
122.
Samer S. El-Kamary Michelle D. Shardell Mohamed Abdel-Hamid Soheir Ismail Mohamed El-Ateek Mohamed Metwally Nabiel Mikhail Mohamed Hashem Amr Mousa Amr Aboul-Fotouh Mohamed El-Kassas Gamal Esmat G. Thomas Strickland 《Phytomedicine》2009,16(5):391-400
PurposeMilk thistle or its purified extract, silymarin (Silybum marianum), is widely used in treating acute or chronic hepatitis. Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures, its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive. In this study, our purpose was to determine whether silymarin improves symptoms, signs and laboratory test results in patients with acute clinical hepatitis, regardless of etiology.MethodsThis is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at two fever hospitals in Tanta and Banha, Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels >2.5 times the upper limit of normal were enrolled. The intervention consisted of three times daily ingestion of either a standard recommended dose of 140 mg of silymarin (Legalon®, MADAUS GmbH, Cologne, Germany), or a vitamin placebo for four weeks with an additional four-week follow-up. The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2, 4 and 7 and weeks 2, 4, and 8. Side-effects and adverse events were ascertained by self-report.ResultsFrom July 2003 through October 2005, 105 eligible patients were enrolled after providing informed consent. No adverse events were noted and both silymarin and placebo were well tolerated. Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013), jaundice (p=0.02) and scleral icterus (p=0.043). There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012), but other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced.ConclusionsPatients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process. 相似文献
123.
Mansour Djedaini Milou-Daniel Drici Perla Saint-Marc Annie Ladoux 《Biochemical and biophysical research communications》2009,386(1):96-100
HIV-protease inhibitors (PIs) markedly decreased mortality of HIV-infected patients. However, their use has been associated with occurence of metabolic abnormalities the causes of which are not well understood. We report here that lopinavir, one of the most prescribed PI, dose-dependently co-induced insulin resistance and ER stress in human adipocytes obtained from differentiation of precursor cells.Insulin resistance was subsequent to IRS1 phosphorylation defects and resulted in a concentration-dependent decrease of glucose uptake. The major ER stress pathway involved was the phosphorylation of eIF2-α. Salubrinal, a selective eIF2-α dephosphorylation inhibitor, induced insulin resistance by targeting IRS1 phosphorylation at serine 312 and acted synergistically with LPV when both drugs were used in combination.This study points out the key role of eIF2-α phosphorylation in the development of PI-associated insulin resistance and ER stress. Thus, this protein represents a promising therapeutic target for development of new PIs devoid of adverse metabolic effects. 相似文献
124.
Philippe Marullo Chantal Mansour Matthieu Dufour Warren Albertin Delphine Sicard Marina Bely & Denis Dubourdieu 《FEMS yeast research》2009,9(8):1148-1160
During red wine fermentation, high temperatures may cause stuck fermentation by affecting the physiology of fermenting yeast. This deleterious effect is the result of the complex interaction of temperature with other physicochemical parameters of grape juice, such as sugar and lipid content. The genetic background of fermenting yeast also interacts with this complex matrix and some strains are more resistant to high temperatures than others. Here, the temperature tolerance of nine commercial starters was evaluated, demonstrating that, at high sugar concentrations, half of them are sensitive to temperature. Using a classical backcross approach, one thermo-sensitive commercial starter was genetically improved by introducing quantitative trait loci conferring resistance to temperature. With this breeding program it is possible to obtain a thermo-resistant strain sharing most of its genome with the initial commercial starter. The parental and improved strains were compared for population growth and fermentation ability in various conditions. Despite their common genetic background, these two strains showed slight physiological differences in response to environmental changes that enable identification of the key physiological parameters influencing stuck fermentation. 相似文献
125.
126.
Kallert DM Bauer W Haas W El-Matbouli M 《International journal for parasitology》2011,41(3-4):271-276
This work reports the discovery of an hitherto unknown chemical recognition trait enabling a parasitic life cycle in aquatic habitats. We believe this is the first record of a natural, host-derived chemical molecule identified as a recognition cue for the phylum Myxozoa. The actinospores of these parasites attach to fish hosts via polar filaments that are extruded upon mechanical stimulation after preceding recognition of a chemical trigger contained in surface mucus. Our goal was to identify this signal. We separated compounds from a purified active fraction derived from trout mucus by a novel HPLC method. By subsequent nuclear magnetic resonance analysis of distinct components and testing in bioassays we elicited stimulation of polar filament discharge and sporoplasm emission in actinospores of three myxozoan spp., Myxobolus cerebralis, Myxobolus pseudodispar and Henneguya nuesslini, by the free nucleosides inosine, 2'-deoxyinosine and guanosine. These nucleosides also activated sporoplasm emission. Nucleosides appear to be appropriate cues for rapid host recognition by the waterborne parasite stages since they are continuously released into surface mucus. The recognition mechanism is not specific for susceptible host species, at least in the myxozoan spp. examined. In addition, a novel function of nucleobase derivatives as semiochemicals was uncovered and a wider impact of this molecule class in parasite recognition systems and aquatic chemical ecology is predicted. The relevance for disease prevention and cell culturing remains to be explored. 相似文献
127.
Wright SW Carlo AA Danley DE Hageman DL Karam GA Mansour MN McClure LD Pandit J Schulte GK Treadway JL Wang IK Bauer PH 《Bioorganic & medicinal chemistry letters》2003,13(12):2055-2058
3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design. 相似文献
128.
Seyed Abbas Hosseinijou Saeed Mansour Mohsen Akbarpour Shirazi 《The International Journal of Life Cycle Assessment》2014,19(3):620-645
Purpose
Sustainability of a material-based product mainly depends on the materials used for the product itself or during its lifetime. A material selection decision should not only capture the functional performance required but should also consider the economical, social, and environmental impacts originated during the product life cycle. There is a need to assess social impacts of materials along the full life cycle, not only to be able to address the “social dimension” in sustainable material selection but also for potentially improving the circumstances of affected stakeholders. This paper presents the method and a case study of social life cycle assessment (S-LCA) specialized for comparative studies. Although the authors’ focus is on material selection, the proposed methodology can be used for comparative assessment of products in general.Methods
The method is based on UNEP/SETAC “guidelines for social life-cycle assessment of products” and includes four main phases: goal and scope definition, life cycle inventory analysis, life cycle impact assessment, and life cycle interpretation. However, some special features are presented to adjust the framework for materials comparison purpose. In life cycle inventory analysis phase, a hot spot assessment is carried out using material flow analysis and stakeholder and experts’ interviews. Based on the results of that, a pairwise comparison method is proposed for life cycle impact assessment applying analytic hierarchy process. A case study was conducted to perform a comparative assessment of the social and socio-economic impacts in life cycle of concrete and steel as building materials in Iran. For hot spot analysis, generic and national level data were gathered, and for impact assessment phase, site-specific data were used.Result and discussion
The unique feature of the proposed method compared with other works in S-LCA is its specialty to materials and products comparison. This leads to some differences in methodological issues of S-LCA that are explained in the paper in detail. The case study results assert that “steel/iron” in the north of Iran generally has the better social performance than “concrete/cement.” However, steel is associated with many negative social effects in some subcategories, e.g., freedom of association, fair salary, and occupational health in extraction phase. Against, social profile of concrete and cement industry is damaged mainly due to the negative impact of cement production on safe and healthy living condition. The case study presented in this article shows that the evaluation of social impacts is possible, even if the assessment is always affected by subjective value systems.Conclusions
Application of the UNEP/SETAC guidelines in comparative studies can be encouraged based on the results of this paper. It enables a hotspot assessment of the social and socio-economic impacts in life cycle of alternative materials. This research showed that the development of a specialized S-LCA approach for materials and products comparison is well underway although many challenges still persist. Particularly characterization method in life cycle impact assessment phase is challenging. The findings of this case study pointed out that social impacts are primarily connected to the conduct of companies and less with processes and materials in general. These findings confirm the results of Dreyer et al. (Int J Life Cycle Assess 11(2):88–97, 2006). The proposed approach aims not only to identify the best socially sustainable alternative but also to reveal product/process improvement potentials to facilitate companies to act socially compatible. It will be interesting to apply the UNEP/SETAC approach of S-LCA to other materials and products; materials with a more complex life cycle will be a special challenge. As with any new method, getting experience on data collection and evaluation, building a data base, integrating the method in software tools, and finding ways for effective communication of results are important steps until integrating S-LCA in routine decision support. 相似文献129.
130.