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41.
Background
The taxonomic name of an organism is a key link between different databases that store information on that organism. However, in the absence of a single, comprehensive database of organism names, individual databases lack an easy means of checking the correctness of a name. Furthermore, the same organism may have more than one name, and the same name may apply to more than one organism. 相似文献42.
Barnes MJ Cooper N Davenport RJ Dyke HJ Galleway FP Galvin FC Gowers L Haughan AF Lowe C Meissner JW Montana JG Morgan T Picken CL Watson RJ 《Bioorganic & medicinal chemistry letters》2001,11(8):1081-1083
The synthesis of a novel series of guanine analogues is reported. The compounds have been assessed in vitro and some analogues have been found to be inhibitors of phosphodiesterase type 7 (PDE7). 相似文献
43.
44.
Charlotte E. Mardle Layla R. Goddard Bailei C. Spelman Helen S. Atkins Louise E. Butt Paul A. Cox Darren M. Gowers Helen A. Vincent Anastasia J. Callaghan 《Biochemistry and Biophysics Reports》2020
Increasing resistance of bacteria to antibiotics is a serious global challenge and there is a need to unlock the potential of novel antibacterial targets. One such target is the essential prokaryotic endoribonuclease RNase E. Using a combination of in silico high-throughput screening and in vitro validation we have identified three novel small molecule inhibitors of RNase E that are active against RNase E from Escherichia coli, Francisella tularensis and Acinetobacter baumannii. Two of the inhibitors are non-natural small molecules that could be suitable as lead compounds for the development of broad-spectrum antibiotics targeting RNase E. The third small molecule inhibitor is glucosamine-6-phosphate, a precursor of bacterial cell envelope peptidoglycans and lipopolysaccharides, hinting at a novel metabolite-mediated mechanism of regulation of RNase E. 相似文献
45.
Alam M Beevers RE Ceska T Davenport RJ Dickson KM Fortunato M Gowers L Haughan AF James LA Jones MW Kinsella N Lowe C Meissner JW Nicolas AL Perry BG Phillips DJ Pitt WR Platt A Ratcliffe AJ Sharpe A Tait LJ 《Bioorganic & medicinal chemistry letters》2007,17(12):3463-3467
The development of a series of novel aminopyrimidines as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay are discussed. 相似文献
46.
Viktorian Miok Saskia M Wilting Mark A van de Wiel Annelieke Jaspers Paula I van Noort Ruud H Brakenhoff Peter JF Snijders Renske DM Steenbergen Wessel N van Wieringen 《BMC bioinformatics》2014,15(1)
Background
To determine which changes in the host cell genome are crucial for cervical carcinogenesis, a longitudinal in vitro model system of HPV-transformed keratinocytes was profiled in a genome-wide manner. Four cell lines affected with either HPV16 or HPV18 were assayed at 8 sequential time points for gene expression (mRNA) and gene copy number (DNA) using high-resolution microarrays. Available methods for temporal differential expression analysis are not designed for integrative genomic studies.Results
Here, we present a method that allows for the identification of differential gene expression associated with DNA copy number changes over time. The temporal variation in gene expression is described by a generalized linear mixed model employing low-rank thin-plate splines. Model parameters are estimated with an empirical Bayes procedure, which exploits integrated nested Laplace approximation for fast computation. Iteratively, posteriors of hyperparameters and model parameters are estimated. The empirical Bayes procedure shrinks multiple dispersion-related parameters. Shrinkage leads to more stable estimates of the model parameters, better control of false positives and improvement of reproducibility. In addition, to make estimates of the DNA copy number more stable, model parameters are also estimated in a multivariate way using triplets of features, imposing a spatial prior for the copy number effect.Conclusion
With the proposed method for analysis of time-course multilevel molecular data, more profound insight may be gained through the identification of temporal differential expression induced by DNA copy number abnormalities. In particular, in the analysis of an integrative oncogenomics study with a time-course set-up our method finds genes previously reported to be involved in cervical carcinogenesis. Furthermore, the proposed method yields improvements in sensitivity, specificity and reproducibility compared to existing methods. Finally, the proposed method is able to handle count (RNAseq) data from time course experiments as is shown on a real data set.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-327) contains supplementary material, which is available to authorized users. 相似文献47.
Billah M Cooper N Cuss F Davenport RJ Dyke HJ Egan R Ganguly A Gowers L Hannah DR Haughan AF Kendall HJ Lowe C Minnicozzi M Montana JG Naylor R Oxford J Peake JC Piwinski JJ Runcie KA Sabin V Sharpe A Shih NY Warneck JB 《Bioorganic & medicinal chemistry letters》2002,12(12):1621-1623
The syntheses and pharmacological profiles of some 2-trifluoromethyl-8-methoxyquinoline-5-carboxamides are described. SCH351591 is a potent selective inhibitor of phosphodiesterase type 4 (PDE4). 相似文献
48.
Buckley G Cooper N Dyke HJ Galleway F Gowers L Gregory JC Hannah DR Haughan AF Hellewell PG Kendall HJ Lowe C Maxey R Montana JG Naylor R Picken CL Runcie KA Sabin V Tuladhar BR Warneck JB 《Bioorganic & medicinal chemistry letters》2000,10(18):2137-2140
The synthesis and pharmacological profile of a novel series of 7-methoxybenzofuran-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4). 相似文献
49.
Bingham AH Davenport RJ Fosbeary R Gowers L Knight RL Lowe C Owen DA Parry DM Pitt WR 《Bioorganic & medicinal chemistry letters》2008,18(12):3622-3627
The synthesis and structure-activity relationship of a novel series of aminopyrimidines are exemplified. Results of key compounds from within this series in the E-selectin reporter cell assay are also reported. 相似文献
50.
Buckley GM Fosbeary R Fraser JL Gowers L Higueruelo AP James LA Jenkins K Mack SR Morgan T Parry DM Pitt WR Rausch O Richard MD Sabin V 《Bioorganic & medicinal chemistry letters》2008,18(12):3656-3660
Following the identification of a potent IRAK inhibitor through routine project cross screening, a novel class of IRAK-4 inhibitor was established. The SAR of imidazo[1,2-a]pyridino-pyridines and benzimidazolo-pyridines was explored. 相似文献