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111.
Local genes for local bacteria: Evidence of allopatry in the genomes of transatlantic Campylobacter populations 下载免费PDF全文
Ben Pascoe Guillaume Méric Koji Yahara Helen Wimalarathna Susan Murray Matthew D. Hitchings Emma L. Sproston Catherine D. Carrillo Eduardo N. Taboada Kerry K. Cooper Steven Huynh Alison J. Cody Keith A. Jolley Martin C. J. Maiden Noel D. McCarthy Xavier Didelot Craig T. Parker Samuel K. Sheppard 《Molecular ecology》2017,26(17):4497-4508
The genetic structure of bacterial populations can be related to geographical locations of isolation. In some species, there is a strong correlation between geographical distance and genetic distance, which can be caused by different evolutionary mechanisms. Patterns of ancient admixture in Helicobacter pylori can be reconstructed in concordance with past human migration, whereas in Mycobacterium tuberculosis it is the lack of recombination that causes allopatric clusters. In Campylobacter, analyses of genomic data and molecular typing have been successful in determining the reservoir host species, but not geographical origin. We investigated biogeographical variation in highly recombining genes to determine the extent of clustering between genomes from geographically distinct Campylobacter populations. Whole‐genome sequences from 294 Campylobacter isolates from North America and the UK were analysed. Isolates from within the same country shared more recently recombined DNA than isolates from different countries. Using 15 UK/American closely matched pairs of isolates that shared ancestors, we identify regions that have frequently and recently recombined to test their correlation with geographical origin. The seven genes that demonstrated the greatest clustering by geography were used in an attribution model to infer geographical origin which was tested using a further 383 UK clinical isolates to detect signatures of recent foreign travel. Patient records indicated that in 46 cases, travel abroad had occurred <2 weeks prior to sampling, and genomic analysis identified that 34 (74%) of these isolates were of a non‐UK origin. Identification of biogeographical markers in Campylobacter genomes will contribute to improved source attribution of clinical Campylobacter infection and inform intervention strategies to reduce campylobacteriosis. 相似文献
112.
113.
Dynamic localization of HmpF regulates type IV pilus activity and directional motility in the filamentous cyanobacterium Nostoc punctiforme 下载免费PDF全文
Ye Won Cho Alfonso Gonzales Thomas V. Harwood Jessica Huynh Yeji Hwang Jun Sang Park Anthony Q. Trieu Parth Italia Vivek K. Pallipuram Douglas D. Risser 《Molecular microbiology》2017,106(2):252-265
Many cyanobacteria exhibit surface motility powered by type 4 pili (T4P). In the model filamentous cyanobacterium Nostoc punctiforme, the T4P systems are arrayed in static, bipolar rings in each cell. The chemotaxis‐like Hmp system is essential for motility and the coordinated polar accumulation of PilA on cells in motile filaments, while the Ptx system controls positive phototaxis. Using transposon mutagenesis, a gene, designated hmpF, was identified as involved in motility. Synteny among filamentous cyanobacteria and the similar expression patterns for hmpF and hmpD imply that HmpF is part of the Hmp system. Deletion of hmpF produced a phenotype distinct from other hmp genes, but indistinguishable from pilB or pilQ. Both an HmpF‐GFPuv fusion protein, and PilA, as assessed by in situ immunofluorescence, displayed coordinated, unipolar localization at the leading pole of each cell. Reversals were modulated by changes in light intensity and preceded by the migration of HmpF‐GFPuv to the lagging cell poles. These results are consistent with a model where direct interaction between HmpF and the T4P system activates pilus extension, the Hmp system facilitates coordinated polarity of HmpF to establish motility, and the Ptx system modulates HmpF localization to initiate reversals in response to changes in light intensity. 相似文献
114.
Ngo JC Giang K Chakrabarti S Ma CT Huynh N Hagopian JC Dorrestein PC Fu XD Adams JA Ghosh G 《Molecular cell》2008,29(5):563-576
The 2.9 A crystal structure of the core SRPK1:ASF/SF2 complex reveals that the N-terminal half of the basic RS domain of ASF/SF2, which is destined to be phosphorylated, is bound to an acidic docking groove of SRPK1 distal to the active site. Phosphorylation of ASF/SF2 at a single site in the C-terminal end of the RS domain generates a primed phosphoserine that binds to a basic site in the kinase. Biochemical experiments support a directional sliding of the RS peptide through the docking groove to the active site during phosphorylation, which ends with the unfolding of a beta strand of the RRM domain and binding of the unfolded region to the docking groove. We further suggest that the priming of the first serine facilitates directional substrate translocation and efficient phosphorylation. 相似文献
115.
Purandare AV Chen Z Huynh T Pang S Geng J Vaccaro W Poss MA Oconnell J Nowak K Jayaraman L 《Bioorganic & medicinal chemistry letters》2008,18(15):4438-4441
This study reports the identification and Hits to Leads optimization of inhibitors of coactivator associated arginine methyltransferase (CARM1). Compound 7b is a potent, selective inhibitor of CARM1. 相似文献
116.
Ohn Nyunt Joyce Y Wu Ivan N McGown Mark Harris Tony Huynh Gary M Leong David M Cowley Andrew M Cotterill 《The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists》2009,30(2):67-74
Maturity Onset Diabetes of Young (MODY) is a monogenic and autosomal dominant form of diabetes mellitus with onset of the disease often before 25 years of age. It is due to dysfunction of pancreatic ß cells characterised by non-ketotic diabetes and absence of pancreatic auto-antibodies. It is frequently mistaken for type 1 or type 2 diabetes mellitus. Diagnosis of MODY is important as the GCK subtype has better prognosis and may not require any treatment. Subtypes HNF1A and HNF4A are sensitive to sulfonylureas, however diabetes complications are common if not treated early. Moreover, there is genetic implication for the patient and family. Rare MODY subtypes can be associated with pancreatic and renal anomalies as well as exocrine dysfunction of the pancreas. So far there are six widely accepted subtypes of MODY described but the list has grown to nine. Although the majority of diabetes mellitus in youth remains type 1 and the incidence of type 2 is rising, MODY should be considered in patients with non-ketotic diabetes at presentation, and in patients with a strong family history of diabetes mellitus without pancreatic auto-antibodies. Furthermore the diagnosis must be confirmed by molecular studies. With advancement in genomic technology, rapid screening for MODY mutations will become readily available in the future. 相似文献
117.
Tram Huynh Zhong Chen Suhong Pang Jieping Geng Tiziano Bandiera Simona Bindi Paola Vianello Fulvia Roletto Sandrine Thieffine Arturo Galvani Wayne Vaccaro Michael A. Poss George L. Trainor Matthew V. Lorenzi Marco Gottardis Lata Jayaraman Ashok V. Purandare 《Bioorganic & medicinal chemistry letters》2009,19(11):2924-2927
Design, synthesis, and SAR development led to the identification of the potent, novel, and selective pyrazole based inhibitor (7f) of Coactivator Associated Arginine Methyltransferase (CARM1). 相似文献
118.
Discovery of novel dihydro-9,10-ethano-anthracene carboxamides as glucocorticoid receptor modulators
Bingwei V. Yang Wayne Vaccaro Arthur M. Doweyko Lidia M. Doweyko Tram Huynh David Tortolani Steven G. Nadler Lorraine McKay John Somerville Deborah A. Holloway Sium Habte David S. Weinstein Joel C. Barrish 《Bioorganic & medicinal chemistry letters》2009,19(8):2139-2143
A series of dihydro-9,10-ethano-anthracene-11-carboxamides as novel glucocorticoid receptor modulators is reported. SAR exploration identified compounds from this series displaying a promising dissociation profile in discriminating between transrepression and transactivation activities. 17a is a partial agonist of GR-mediated transactivation which elicits potent and efficacious transrepression in reporter gene assays. A hypothetical binding mode is provided which accounts for the induction of functional activity by a bridgehead methyl group. 相似文献
119.
Constance Schultsz Nguyen Van Dung Le Thanh Hai Do Quang Ha J. S. Malik Peiris Wilina Lim Jean-Michel Garcia Nguyen Dac Tho Nguyen Thi Hoang Lan Huynh Huu Tho Phan Xuan Thao H. Rogier van Doorn Nguyen Van Vinh Chau Jeremy Farrar Menno D. de Jong 《PloS one》2009,4(11)
Background
Between 2003 and 2005, highly pathogenic avian influenza A (H5N1) viruses caused large scale outbreaks in poultry in the Ho Chi Minh City area in Vietnam. We studied the prevalence of antibodies against H5N1 in poultry workers and cullers who were active in the program in Ho Chi Minh City in 2004 and 2005.Methodology/Principal Findings
Single sera from 500 poultry workers and poultry cullers exposed to infected birds were tested for antibodies to avian influenza H5N1, using microneutralization assays and hemagglutination inhibition assay with horse blood. All sera tested negative using microneutralization tests. Three samples showed a 1∶80 titer in the hemagglutination inhibition assay.Conclusions/Significance
This study provides additional support for the low transmissibility of clade 1 H5N1 to humans, but limited transmission to highly exposed persons cannot be excluded given the presence of low antibody titers in some individuals. 相似文献120.
Duong P. Huynh Marwan Maalouf Alcino J. Silva Felix E. Schweizer Stefan M. Pulst 《PloS one》2009,4(7)
Mouse models with physiological and behavioral differences attributable to differential plasticity of hippocampal and amygdalar neuronal networks are rare. We previously generated ataxin-2 (Atxn2) knockout mice and demonstrated that these animals lacked obvious anatomical abnormalities of the CNS, but showed marked obesity and reduced fertility. We now report on behavioral changes as a consequence of Atxn2-deficiency. Atxn2-deficiency was associated with impaired long-term potentiation (LTP) in the amygdala, but normal LTP in the hippocampus. Intact hippocampal plasticity was associated behaviorally with normal Morris Water maze testing. Impaired amygdala plasticity was associated with reduced cued and contextual fear conditioning. Conditioned taste aversion, however, was normal. In addition, knockout mice showed decreased innate fear in several tests and motor hyperactivity in open cage testing. Our results suggest that Atxn2-deficiency results in a specific set of behavioral and cellular disturbances that include motor hyperactivity and abnormal fear-related behaviors, but intact hippocampal function. This animal model may be useful for the study of anxiety disorders and should encourage studies of anxiety in patients with spinocerebellar ataxia type 2 (SCA2). 相似文献