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排序方式: 共有536条查询结果,搜索用时 62 毫秒
121.
Aymeric Chartier Pierre Klein Stéphanie Pierson Nicolas Barbezier Teresa Gidaro Fran?ois Casas Steven Carberry Paul Dowling Laurie Maynadier Ma?lle Bellec Martine Oloko Claude Jardel Bodo Moritz George Dickson Vincent Mouly Kay Ohlendieck Gillian Butler-Browne Capucine Trollet Martine Simonelig 《PLoS genetics》2015,11(3)
Oculopharyngeal muscular dystrophy (OPMD), a late-onset disorder characterized by progressive degeneration of specific muscles, results from the extension of a polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). While the roles of PABPN1 in nuclear polyadenylation and regulation of alternative poly(A) site choice are established, the molecular mechanisms behind OPMD remain undetermined. Here, we show, using Drosophila and mouse models, that OPMD pathogenesis depends on affected poly(A) tail lengths of specific mRNAs. We identify a set of mRNAs encoding mitochondrial proteins that are down-regulated starting at the earliest stages of OPMD progression. The down-regulation of these mRNAs correlates with their shortened poly(A) tails and partial rescue of their levels when deadenylation is genetically reduced improves muscle function. Genetic analysis of candidate genes encoding RNA binding proteins using the Drosophila OPMD model uncovers a potential role of a number of them. We focus on the deadenylation regulator Smaug and show that it is expressed in adult muscles and specifically binds to the down-regulated mRNAs. In addition, the first step of the cleavage and polyadenylation reaction, mRNA cleavage, is affected in muscles expressing alanine-expanded PABPN1. We propose that impaired cleavage during nuclear cleavage/polyadenylation is an early defect in OPMD. This defect followed by active deadenylation of specific mRNAs, involving Smaug and the CCR4-NOT deadenylation complex, leads to their destabilization and mitochondrial dysfunction. These results broaden our understanding of the role of mRNA regulation in pathologies and might help to understand the molecular mechanisms underlying neurodegenerative disorders that involve mitochondrial dysfunction. 相似文献
122.
Redondo-Nieto M Barret M Morrisey JP Germaine K Martínez-Granero F Barahona E Navazo A Sánchez-Contreras M Moynihan JA Giddens SR Coppoolse ER Muriel C Stiekema WJ Rainey PB Dowling D O'Gara F Martín M Rivilla R 《Journal of bacteriology》2012,194(5):1273-1274
Pseudomonas fluorescens F113 is a plant growth-promoting rhizobacterium (PGPR) that has biocontrol activity against fungal plant pathogens and is a model for rhizosphere colonization. Here, we present its complete genome sequence, which shows that besides a core genome very similar to those of other strains sequenced within this species, F113 possesses a wide array of genes encoding specialized functions for thriving in the rhizosphere and interacting with eukaryotic organisms. 相似文献
123.
Dakin LA Block MH Chen H Code E Dowling JE Feng X Ferguson AD Green I Hird AW Howard T Keeton EK Lamb ML Lyne PD Pollard H Read J Wu AJ Zhang T Zheng X 《Bioorganic & medicinal chemistry letters》2012,22(14):4599-4604
Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferative, and selectivity data. 相似文献
124.
Reduced expression of regucalcin in young and aged mdx diaphragm indicates abnormal cytosolic calcium handling in dystrophin-deficient muscle 总被引:1,自引:0,他引:1
Doran P Dowling P Donoghue P Buffini M Ohlendieck K 《Biochimica et biophysica acta》2006,1764(4):773-785
The cytosolic Ca2+ -binding protein regucalcin is involved in intracellular signaling and present in high abundance in the liver. Here, we could show by comparative mass spectrometry-based proteomics screening of normal versus dystrophic fibres that regucalcin of 33.9 kDa and pI5.2 also exists in diaphragm muscle. Since the expression of sarcolemmal Ca2+ -leak channels and luminal Ca2+ -binding elements is altered in dystrophin-deficient muscle, we initiated this study in order to determine whether additional soluble muscle proteins involved in Ca2+ -handling are affected in muscular dystrophy. Following separation by two-dimensional gel electrophoresis, the spot pattern of the normal versus the mdx diaphragm muscle proteome was evaluated by densitometry. The expression levels of 20 major protein spots were shown to change and their identity determined by mass spectrometry. A 2-fold reduction of regucalcin in mdx diaphragm, as well as in dystrophic limb muscle and heart, was confirmed by immunoblotting in both young and aged mdx mice. The results from our proteomics analysis of dystrophic diaphragm support the concept that abnormal Ca2+ -handling is involved in x-linked muscular dystrophy. The reduction in key Ca2+ -handling proteins may result in an insufficient maintenance of Ca2+ -homeostasis and an abnormal regulation of Ca2+ -dependent enzymes resulting in disturbed intracellular signaling mechanisms in dystrophinopathies. 相似文献
125.
126.
The Squalius alburnoides complex was produced by hybridization between female S. pyrenaicus (PP genome) and an hypothetical paternal ancestor related with Anaecypris hispanica (AA genome). This study examined a diversity of mating types and found that there is the potential for considerable gene exchange among diploid, triploid and tetraploid hybrids. Using microsatellites, genomes were attributed to Squalius pyrenaicus (P) or reconstituted “nuclear non-hybrid” S. alburnoides (A), and subsequently confirmed in hybrids. Recombination of AA genomes in the “nuclear non-hybrid males” and recombination of the homogametic genomes (AA or PP) after exclusion of the heterogametic genome in triploid females (PAA) were observed by analysing parents and progeny of breeding experiments. Reproduction of tetraploids, generating a symmetric tetraploid genotype (PPAA) in the progeny, suggests a process that could potentially lead to the formation of a new bisexual species. Present results also support: (i) previously hypothesized pathways, in which PPA S. alburnoides females exclude the A genome, exhibit meiotic recombination between the P genomes and generate haploid eggs; (ii) reconstitution of the diploid maternal ancestor genome (PP) as well as of the unknown paternal ancestor (AA); (iii) the occurrence of the same genomic reproductive mechanisms when Anaecypris hispanica is involved; and (iv) the existence of an A. hispanica-like ancestor as the paternal ancestor of S. alburnoides. 相似文献
127.
Martina McGuinness Claire Ivory Niamh Gilmartin David N. Dowling 《International biodeterioration & biodegradation》2006,58(3-4):203
The bphK gene located in the bph operon of Burkholderia LB400 encodes a protein, BphKLB400, with significant sequence similarity to glutathione-S-transferases (GST), a group of enzymes involved in the detoxification of many endobiotic and xenobiotic substances. Comparison of the amino acid sequence of BphKLB400 with GST from other polychlorinated biphenyl (PCB)-degrading bacteria identified a number of highly conserved amino acids in the C-terminal region of the protein that may be associated with substrate specificity. In this study, two of these conserved amino acids in BphKLB400 (amino acids 152 and 180) were selected for mutation, using site-directed mutagenesis, and substrate specificity assays. BphKLB400 (wildtype and mutant) was over-expressed in Escherichia coli where the bphK gene (wildtype and mutant) is under the expression of a lac promoter and is induced by isopropyl thiogalactoside, and bacterial cell extracts were prepared for GST activity assays. Mutations at amino acids 152 and 180 were shown to affect GST activity of BphKLB400 using 1-chloro-2,4-dinitrobenzene, the model substrate for GST activity assays; 4-chlorobenzoate and 3-chlorobenzoate, intermediates in the polychlorinated biphenyl (PCB) degradation pathway, and 2,4-dichlorophenoxyacetate and atrazine, commonly used herbicides; as substrates. A BphKLB400 mutant (Ala180Pro) is identified in this study as having increased activity towards all substrates tested. This mutant may have potential in bioremediation. 相似文献
128.
129.
Most asexual fungal symbionts of grasses in the genus Neotyphodium occurring in nature are of hybrid origin. Most hybrid Neotyphodium species result from interspecific hybridization events between pathogenic Epichloë species or co-occurring non-hybrid Neotyphodium species. Current hypotheses for the prevalence of hybrid Neotyphodium species include reduction of mutation accumulation and increased adaptive response to environmental extremes. We tested the adaptive response hypothesis by characterizing the distribution of uninfected, hybrid, and non-hybrid Neotyphodium endophytes in 24 native Arizona fescue host populations and abiotic parameters at each locality. Infection was high in all host populations (>70%), but the majority of host populations were infected by non-hybrid Neotyphodium (>50% on average). Principal component analysis indicates the frequency of plants infected with hybrid fungi is negatively related to soil nutrients and positively correlated with early spring moisture. Non-hybrid infected hosts are positively associated with soil nutrients and show a complex relationship with soil moisture (negative in early spring moisture, positive with late summer soil moisture). These results suggest the frequency of uninfected, hybrid, and non-hybrid infected plants is related to resource availability and abiotic stress factors. This supports the hypothesis that hybridization in asexual fungal symbionts increases host adaptability to extreme environments. 相似文献
130.
Shelley N. Facente Teri Dowling Eric Vittinghoff Deanna L. Sykes Grant N. Colfax 《PloS one》2009,4(12)