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121.
Alan McNally Yaara Oren Darren Kelly Ben Pascoe Steven Dunn Tristan Sreecharan Minna Vehkala Niko V?lim?ki Michael B. Prentice Amgad Ashour Oren Avram Tal Pupko Ulrich Dobrindt Ivan Literak Sebastian Guenther Katharina Schaufler Lothar H. Wieler Zong Zhiyong Samuel K. Sheppard James O. McInerney Jukka Corander 《PLoS genetics》2016,12(9)
The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug–resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements. 相似文献
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123.
Niko Braun Peter Fritz Christoph Ulmer Joerg Latus Martin Kimmel Dagmar Biegger German Ott Fabian Reimold Klaus-Peter Thon Juergen Dippon Stephan Segerer M. Dominik Alscher 《PloS one》2012,7(11)
Background
The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPSMethods
We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients.Results
The following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%.Conclusion
The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database. 相似文献124.
125.
Computational methods for the design of effective therapies against drug resistant HIV strains 总被引:3,自引:0,他引:3
Beerenwinkel N Sing T Lengauer T Rahnenführer J Roomp K Savenkov I Fischer R Hoffmann D Selbig J Korn K Walter H Berg T Braun P Fätkenheuer G Oette M Rockstroh J Kupfer B Kaiser R Däumer M 《Bioinformatics (Oxford, England)》2005,21(21):3943-3950
The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure exerted by the human immune system and by combination drug therapy. We have developed several computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genomic data. 相似文献
126.
Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1 总被引:7,自引:0,他引:7 下载免费PDF全文
127.
128.
Francesca Di Giallonardo Armin T?pfer Melanie Rey Sandhya Prabhakaran Yannick Duport Christine Leemann Stefan Schmutz Nottania K. Campbell Beda Joos Maria Rita Lecca Andrea Patrignani Martin D?umer Christian Beisel Peter Rusert Alexandra Trkola Huldrych F. Günthard Volker Roth Niko Beerenwinkel Karin J. Metzner 《Nucleic acids research》2014,42(14):e115
Next-generation sequencing (NGS) technologies enable new insights into the diversity of virus populations within their hosts. Diversity estimation is currently restricted to single-nucleotide variants or to local fragments of no more than a few hundred nucleotides defined by the length of sequence reads. To study complex heterogeneous virus populations comprehensively, novel methods are required that allow for complete reconstruction of the individual viral haplotypes. Here, we show that assembly of whole viral genomes of ∼8600 nucleotides length is feasible from mixtures of heterogeneous HIV-1 strains derived from defined combinations of cloned virus strains and from clinical samples of an HIV-1 superinfected individual. Haplotype reconstruction was achieved using optimized experimental protocols and computational methods for amplification, sequencing and assembly. We comparatively assessed the performance of the three NGS platforms 454 Life Sciences/Roche, Illumina and Pacific Biosciences for this task. Our results prove and delineate the feasibility of NGS-based full-length viral haplotype reconstruction and provide new tools for studying evolution and pathogenesis of viruses. 相似文献
129.
Armin T?pfer Tobias Marschall Rowena A. Bull Fabio Luciani Alexander Sch?nhuth Niko Beerenwinkel 《PLoS computational biology》2014,10(3)
Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the structure of a viral quasispecies from next-generation sequencing data as obtained from bulk sequencing of mixed virus samples. We develop a statistical model for paired-end reads accounting for mutations, insertions, and deletions. Using an iterative maximal clique enumeration approach, read pairs are assembled into haplotypes of increasing length, eventually enabling global haplotype assembly. The performance of our quasispecies assembly method is assessed on simulated data for varying population characteristics and sequencing technology parameters. Owing to its paired-end handling, HaploClique compares favorably to state-of-the-art haplotype inference methods. It can reconstruct error-free full-length haplotypes from low coverage samples and detect large insertions and deletions at low frequencies. We applied HaploClique to sequencing data derived from a clinical hepatitis C virus population of an infected patient and discovered a novel deletion of length 357±167 bp that was validated by two independent long-read sequencing experiments. HaploClique is available at https://github.com/armintoepfer/haploclique. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5. 相似文献
130.
Niko L. Set?l? Juha M. Holopainen Jari Metso Gebrenegus Yohannes Jaakko Hiidenhovi Leif C. Andersson Ove Eriksson Alexandra Robciuc Matti Jauhiainen 《Journal of lipid research》2010,51(11):3126-3134
In addition to circulation, where it transfers phospholipids between lipoprotein particles, phospholipid transfer protein (PLTP) was also identified as a component of normal tear fluid. The purpose of this study was to clarify the secretion route of tear fluid PLTP and elucidate possible interactions between PLTP and other tear fluid proteins. Human lacrimal gland samples were stained with monoclonal antibodies against PLTP. Heparin-Sepharose (H-S) affinity chromatography was used for specific PLTP binding, and coeluted proteins were identified with MALDI-TOF mass spectrometry or Western blot analysis. Immunoprecipitation assay and blotting with specific antibodies helped to identify and characterize PLTP-mucin interaction in tear fluid. Human tear fluid PLTP is secreted from the lacrimal gland. MALDI-TOF analysis of H-S fractions identified several candidate proteins, but protein-protein interaction assays revealed only ocular mucins as PLTP interaction partners. We suggest a dual role for PLTP in human tear fluid: (1) to scavenge lipophilic substances from ocular mucins and (2) to maintain the stability of the anterior tear lipid film. PLTP may also play a role in the development of ocular surface disease. 相似文献