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121.
Kralt D Light B Cheang M MacNair T Wiebe L Limerick B Sarsfield P Hammond G MacDonald K Trepman E Embil JM 《Mycopathologia》2009,167(3):115-124
Background Blastomycosis is an uncommon granulomatous infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. The most frequent clinical infections involve the lung, skin, and bone. Pulmonary manifestations range from asymptomatic
self-limited infection to severe diffuse pneumonia causing respiratory failure.
Objectives To establish the clinical characteristics and outcomes of patients with pulmonary blastomycosis diagnosed at hospitals in
Manitoba and northwestern Ontario, Canada.
Methods A retrospective review of medical records was done for 318 patients with blastomycosis in these regions.
Results The majority of patients were Caucasian (198 (62.5%) patients), male (193 (61%) patients), and residents of Ontario (209 (65.7%)
patients). Most patients were treated in an inpatient hospital ward (266 (84%) patients) and survived (294 (92%) patients).
Pulmonary involvement, either alone or associated with other sites, was present in 296 (93%) of the 318 patients; 22 (7%)
patients had no evidence of pulmonary blastomycosis. The majority of patients had localized lung disease (1–3 quadrants on
chest radiograph involved; 225 (82%) patients). Of 294 (92%) patients requiring hospitalization, 266 (90%) patients received
all inpatient care on a general medical ward; 28 (10%) patients received some care in the intensive care unit (ICU). Factors
associated with ICU admission included diffuse pulmonary disease (four quadrants involved on chest radiograph), diabetes,
and prior use of antimicrobial therapy. Twenty-four (8%) patients died, and multivariate analysis showed that older age and
Aboriginal ethnicity were the significant risk factors for death from blastomycosis.
Conclusion Blastomycosis is a cause of serious, potentially life-threatening pulmonary infection in this geographic region.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
122.
The mechanism by which we age has sparked a huge number of theories, and is an area of intense debate. As the elderly population rises, the importance of elucidating these mechanisms is becoming more apparent as age is the single biggest risk factor for a number of diseases such as cancer, diabetes and neurodegenerative disease. Mitochondrial DNA (MtDNA) mutations have been shown to accumulate in cells and tissues during the ageing process; however the question as to whether these mutations have a causal role in the ageing process remains an area of uncertainty. Here we review the current literature, and discuss the evidence for and against a causal role of mtDNA mutations in ageing and in the pathogenesis of age-related disease. 相似文献
123.
Scott E. Wolkenberg Zhijian Zhao David D. Wisnoski William H. Leister Julie O’Brien Wei Lemaire David L. Williams Marlene A. Jacobson Cyrille Sur Gene G. Kinney Doug J. Pettibone Philip R. Tiller Sheri Smith Christopher Gibson Bennett K. Ma Stacey L. Polsky-Fisher Craig W. Lindsley George D. Hartman 《Bioorganic & medicinal chemistry letters》2009,19(5):1492-1495
Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is discussed. 相似文献
124.
Ryan Tewhey Masakazu Nakano Xiaoyun Wang Carlos Pabón-Peña Barbara Novak Angelica Giuffre Eric Lin Scott Happe Doug N Roberts Emily M LeProust Eric J Topol Olivier Harismendy Kelly A Frazer 《Genome biology》2009,10(10):1-13
Background
Genome sequences, now available for most pathogens, hold promise for the rational design of new therapies. However, biological resources for genome-scale identification of gene function (notably genes involved in pathogenesis) and/or genes essential for cell viability, which are necessary to achieve this goal, are often sorely lacking. This holds true for Neisseria meningitidis, one of the most feared human bacterial pathogens that causes meningitis and septicemia.Results
By determining and manually annotating the complete genome sequence of a serogroup C clinical isolate of N. meningitidis (strain 8013) and assembling a library of defined mutants in up to 60% of its non-essential genes, we have created NeMeSys, a biological resource for Neisseria meningitidis systematic functional analysis. To further enhance the versatility of this toolbox, we have manually (re)annotated eight publicly available Neisseria genome sequences and stored all these data in a publicly accessible online database. The potential of NeMeSys for narrowing the gap between sequence and function is illustrated in several ways, notably by performing a functional genomics analysis of the biogenesis of type IV pili, one of the most widespread virulence factors in bacteria, and by identifying through comparative genomics a complete biochemical pathway (for sulfur metabolism) that may potentially be important for nasopharyngeal colonization.Conclusions
By improving our capacity to understand gene function in an important human pathogen, NeMeSys is expected to contribute to the ongoing efforts aimed at understanding a prokaryotic cell comprehensively and eventually to the design of new therapies. 相似文献125.
Amy K. Reeve Kim J. Krishnan Geoffrey Taylor Joanna L. Elson reas Bender Robert W. Taylor Christopher M. Morris Doug M. Turnbull 《Aging cell》2009,8(4):496-498
Clonally expanded mitochondrial DNA (mtDNA) deletions accumulate with age in human substantia nigra (SN) and high levels cause respiratory chain deficiency. In other human tissues, mtDNA point mutations clonally expand with age. Here, the abundance of mtDNA point mutations within single SN neurons from aged controls was investigated. From 31 single cytochrome c oxidase normal SN neurons, only one clonally expanded mtDNA point mutation was identified, suggesting in these neurons mtDNA point mutations occur rarely, whereas mtDNA deletions are frequently observed. This contrasts observations in mitotic tissues and suggests that different forms of mtDNA maintenance may exist in these two cell types. 相似文献
126.
127.
Zhao Z O'Brien JA Lemaire W Williams DL Jacobson MA Sur C Pettibone DJ Tiller PR Smith S Hartman GD Wolkenberg SE Lindsley CW 《Bioorganic & medicinal chemistry letters》2006,16(23):5968-5972
This Letter describes the synthesis and SAR, developed through an iterative analog library approach, of potent and selective non-sarcosine-derived GlyT1 inhibitors. 相似文献
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129.