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161.
162.
Gloria Brea-Calvo Tobias?B. Haack Daniela Karall Akira Ohtake Federica Invernizzi Rosalba Carrozzo Laura Kremer Sabrina Dusi Christine Fauth Sabine Scholl-Bürgi Elisabeth Graf Uwe Ahting Nicoletta Resta Nicola Laforgia Daniela Verrigni Yasushi Okazaki Masakazu Kohda Diego Martinelli Peter Freisinger Tim?M. Strom Thomas Meitinger Costanza Lamperti Atilano Lacson Placido Navas Johannes?A. Mayr Enrico Bertini Kei Murayama Massimo Zeviani Holger Prokisch Daniele Ghezzi 《American journal of human genetics》2015,96(2):309-317
Primary coenzyme Q10 (CoQ10) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved in CoQ10 biosynthesis. CoQ10 is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to complex III. By whole-exome sequencing, we identified five individuals carrying biallelic mutations in COQ4. The precise function of human COQ4 is not known, but it seems to play a structural role in stabilizing a multiheteromeric complex that contains most of the CoQ10 biosynthetic enzymes. The clinical phenotypes of the five subjects varied widely, but four had a prenatal or perinatal onset with early fatal outcome. Two unrelated individuals presented with severe hypotonia, bradycardia, respiratory insufficiency, and heart failure; two sisters showed antenatal cerebellar hypoplasia, neonatal respiratory-distress syndrome, and epileptic encephalopathy. The fifth subject had an early-onset but slowly progressive clinical course dominated by neurological deterioration with hardly any involvement of other organs. All available specimens from affected subjects showed reduced amounts of CoQ10 and often displayed a decrease in CoQ10-dependent ETC complex activities. The pathogenic role of all identified mutations was experimentally validated in a recombinant yeast model; oxidative growth, strongly impaired in strains lacking COQ4, was corrected by expression of human wild-type COQ4 cDNA but failed to be corrected by expression of COQ4 cDNAs with any of the mutations identified in affected subjects. COQ4 mutations are responsible for early-onset mitochondrial diseases with heterogeneous clinical presentations and associated with CoQ10 deficiency. 相似文献
163.
Lorenzo Marini Robert A. Haack Robert J. Rabaglia Edoardo Petrucco Toffolo Andrea Battisti Massimo Faccoli 《Biological invasions》2011,13(10):2275-2288
Although invasion of exotic ambrosia beetles (fungus feeders) and bark beetles (phloem feeders) (Coleoptera: Curculionidae:
Scolytinae) is considered a major threat to forest health worldwide, no studies have quantitatively investigated the anthropogenic
and environmental factors shaping the biogeographical patterns of invasion by these insects across large spatial scales. The
primary aim of this study was to assess the relative importance of international trade and several environmental variables
of the recipient region on species richness of established exotic Scolytinae. As a reference, we also evaluated the relationships
between the same environmental variables and species richness of native Scolytinae. Using an information-theoretic framework for model selection and hierarchical partitioning, we evaluated the relative importance of the potential drivers of species
richness of native and exotic Scolytinae in 20 European countries and the 48 contiguous continental US states. Analyses were
conducted separately for ambrosia and bark beetle species. Value of imports was a strong predictor of the number of exotic
Scolytinae species in both regions. In addition, in the USA, warmer and wetter climate was positively linked to increased
numbers of both native and exotic ambrosia beetles. Forest heterogeneity and climatic heterogeneity and secondarily forest
area were key drivers in explaining patterns of species richness for native bark beetles but not for exotic species in both
regions. Our findings suggest that if current infestation levels continue on imported plants and wood packaging material,
increasing international trade will likely lead to more establishments of exotic Scolytinae with concomitant negative effects
on forest health in both Europe and the USA. Compared to Europe the risk of invasion appears higher in the USA, especially
for ambrosia beetles in the southeastern USA where the climate appears highly suitable for exotic establishment. 相似文献
164.
SEBASTIÁN APESTEGUÍA RAÚL O. GÓMEZ GUILLERMO W. ROUGIER 《Zoological Journal of the Linnean Society》2012,166(2):342-360
Herein we describe a new rhynchocephalian taxon from the Middle Jurassic of Patagonia, Argentina, representing the first Jurassic record of the group in South America. The new taxon, consisting of a complete dentary, is ascribed to Sphenodontia based on the presence of a deep and wide Meckelian groove, long posterior process, well‐developed coronoid process, and acrodont teeth showing dental regionalization including successional, alternate hatchling, and additional series. This allocation is reinforced by a phylogenetic analysis that places the new taxon in a basal position within a clade of sphenodontians that excludes Diphydontosaurus and Planocephalosaurus. Additionally, the new taxon clusters within a Gondwanan clade with the Indian Godavarisaurus from the Jurassic Kota Formation, sharing the presence of recurved and relatively large posterior successional teeth that are ribbed and bear a peculiar anterolingual groove. This sister‐group relationship is intriguing from a palaeobiogeographical viewpoint, as it suggests some degree of endemism during the initial stages of the breakup of Pangaea. We also discuss the ontogenetic stage of the new taxon and provide insights on the evolution of successional dentition in rhynchocephalians. © 2012 The Linnean Society of London, Zoological Journal of the Linnean Society, 2012, 166 , 342–360. 相似文献
165.
Anthony G. Comuzzie Shelley A. Cole Sandra L. Laston V. Saroja Voruganti Karin Haack Richard A. Gibbs Nancy F. Butte 《PloS one》2012,7(12)
Genetic variants responsible for susceptibility to obesity and its comorbidities among Hispanic children have not been identified. The VIVA LA FAMILIA Study was designed to genetically map childhood obesity and associated biological processes in the Hispanic population. A genome-wide association study (GWAS) entailed genotyping 1.1 million single nucleotide polymorphisms (SNPs) using the Illumina Infinium technology in 815 children. Measured genotype analysis was performed between genetic markers and obesity-related traits i.e., anthropometry, body composition, growth, metabolites, hormones, inflammation, diet, energy expenditure, substrate utilization and physical activity. Identified genome-wide significant loci: 1) corroborated genes implicated in other studies (MTNR1B, ZNF259/APOA5, XPA/FOXE1 (TTF-2), DARC, CCR3, ABO); 2) localized novel genes in plausible biological pathways (PCSK2, ARHGAP11A, CHRNA3); and 3) revealed novel genes with unknown function in obesity pathogenesis (MATK, COL4A1). Salient findings include a nonsynonymous SNP (rs1056513) in INADL (p = 1.2E-07) for weight; an intronic variant in MTNR1B associated with fasting glucose (p = 3.7E-08); variants in the APOA5-ZNF259 region associated with triglycerides (p = 2.5-4.8E-08); an intronic variant in PCSK2 associated with total antioxidants (p = 7.6E-08); a block of 23 SNPs in XPA/FOXE1 (TTF-2) associated with serum TSH (p = 5.5E-08 to 1.0E-09); a nonsynonymous SNP (p = 1.3E-21), an intronic SNP (p = 3.6E-13) in DARC identified for MCP-1; an intronic variant in ARHGAP11A associated with sleep duration (p = 5.0E-08); and, after adjusting for body weight, variants in MATK for total energy expenditure (p = 2.7E-08) and in CHRNA3 for sleeping energy expenditure (p = 6.0E-08). Unprecedented phenotyping and high-density SNP genotyping enabled localization of novel genetic loci associated with the pathophysiology of childhood obesity. 相似文献
166.
167.
168.
Background
Ran GTPase has multiple functions during the cell division cycle, including nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. The activity of Ran is determined by both its guanine nucleotide-bound state and its subcellular localization. 相似文献169.
Randa A Abusham RA Noor Zaliha Raja Rahman Abu Bakar Salleh Mahiran Basri 《Microbial cell factories》2009,8(1):20-9
Background
Many researchers have reported on the optimization of protease production; nevertheless, only a few have reported on the optimization of the production of organic solvent-tolerant proteases. Ironically, none has reported on thermostable organic solvent-tolerant protease to date. The aim of this study was to isolate the thermostable organic solvent-tolerant protease and identify the culture conditions which support its production. The bacteria of genus Bacillus are active producers of extra-cellular proteases, and the thermostability of enzyme production by Bacillus species has been well-studied by a number of researchers. In the present study, the Bacillus subtilis strain Rand was isolated from the contaminated soil found in Port Dickson, Malaysia. 相似文献170.
Bader O Schaller M Klein S Kukula J Haack K Mühlschlegel F Korting HC Schäfer W Hube B 《Molecular microbiology》2001,41(6):1431-1444
Candida glabrata has emerged as one of the most common causes of candidosis. In order to identify factors that are necessary for viability and pathogenicity of this fungal pathogen, we analysed the role of the KEX2 gene, which codes for a regulatory endoproteinase that is known to process certain virulence factors in Candida albicans. The KEX2 gene from C. glabrata was cloned and found to have 51% and 62% identity and high structural similarities to the homologous counterparts in C. albicans and Saccharomyces cerevisiae. KEX2 was expressed at all time points investigated during growth in complex medium. In order to investigate the role of this putative regulatory proteinase, Kex2-deficient mutants were produced. In addition to known kex2 phenotypes, such as pH and calcium hypersensitivity, the mutants grew in cellular aggregates and were found to be hypersensitive to several antifungal drugs that target the cell membrane, including azoles, amorolfine and amphotericin B. Ultrastructural investigation after exposure to low doses of itraconazole showed azole-specific alterations such as enlarged vacuoles and proliferation of the cytoplasmatic membrane in the kex2 mutants, but not in the control strains. In contrast, antifungals such as 5-flucytosine and hydroxypyridones inhibited growth of the kex2 mutants and the control strains to the same extent. In an in vitro model of oral candidosis, kex2 mutants showed reduced tissue damage in the presence of itraconazole compared with the control infections. These data suggest that Kex2 is involved in the processing of proteins that are essential for cell surface integrity of C. glabrata. 相似文献