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121.
Optimization of media for the maximum production of xylanase by Aspergillus fumigatus MKUI was carried out using De Meo's fractional factorial design with seven components such as NaNO3, K2HPO4, MgSO4, FeSO4. KCl, peptone and yeast extract. A. fumigatus produced a maximum of 700 U/gds of enzyme after 48 hr of incubation (before optimization). After two steps of optimization, the medium designed favoured a 2.8 fold (1950 U/gds) increase in xylanase production by A. fumigatus. Optimized medium for Aspergillus fumigatus contained (g/l) NaNO3, 15; K2HPO4, 15; MgSO4, 5; FeSO4, 0.009; KCI, 0.5; peptone, 20; and yeast extract, 10. 相似文献
122.
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124.
Megan K. Fuller Denver M. Faulk Nambirajan Sundaram Maxime M. Mahe Kara M. Stout Richard J. von Furstenberg Brian J. Smith Kirk K. McNaughton Noah F. Shroyer Michael A. Helmrath Susan J. Henning 《Cell and tissue research》2013,354(2):441-450
Intestinal stem cells (ISCs) are responsible for renewal of the epithelium both during normal homeostasis and following injury. As such, they have significant therapeutic potential. However, whether ISCs can survive tissue storage is unknown. We hypothesize that, although the majority of epithelial cells might die, ISCs would remain viable for at least 24 h at 4 °C. To explore this hypothesis, jejuna of C57Bl6/J or Lgr5-LacZ mice were removed and either processed immediately or placed in phosphate-buffered saline at 4 °C. Delayed isolation of epithelium was performed after 24, 30, or 48 h storage. At the light microscope level, despite extensive apoptosis of villus epithelial cells, small intestinal crypts remained morphologically intact for 30 h and ISCs were identifiable via Lgr5-LacZ positivity. Electron microscopy showed that ISCs retained high integrity for 24 h. When assessed by flow cytometry, ISCs were more resistant to degeneration than the rest of the epithelium, including neighboring Paneth cells, with higher viability across all time points. Cultured isolated crypts showed no loss of capacity to form complex enteroids after 24 h tissue storage, with efficiencies after 7 days of culture remaining above 80 %. By 30 h storage, efficiencies declined but budding capability was retained. We conclude that, with delay in isolation, ISCs remain viable and retain their proliferative capacity. In contrast, the remainder of the epithelium, including the Paneth cells, exhibits degeneration and programmed cell death. If these findings are recapitulated in human tissue, storage at 4 °C might offer a valuable temporal window for the harvesting of crypts or ISCs for therapeutic application. 相似文献
125.
A decompositional approach to parameter estimation in pathway modeling: a case study of the Akt and MAPK pathways and their crosstalk 总被引:1,自引:0,他引:1
Koh G Teong HF Clément MV Hsu D Thiagarajan PS 《Bioinformatics (Oxford, England)》2006,22(14):e271-e280
Parameter estimation is a critical problem in modeling biological pathways. It is difficult because of the large number of parameters to be estimated and the limited experimental data available. In this paper, we propose a decompositional approach to parameter estimation. It exploits the structure of a large pathway model to break it into smaller components, whose parameters can then be estimated independently. This leads to significant improvements in computational efficiency. We present our approach in the context of Hybrid Functional Petri Net modeling and evolutionary search for parameter value estimation. However, the approach can be easily extended to other modeling frameworks and is independent of the search method used. We have tested our approach on a detailed model of the Akt and MAPK pathways with two known and one hypothesized crosstalk mechanisms. The entire model contains 84 unknown parameters. Our simulation results exhibit good correlation with experimental data, and they yield positive evidence in support of the hypothesized crosstalk between the two pathways. 相似文献
126.
Spada M Pagliardini S Yasuda M Tukel T Thiagarajan G Sakuraba H Ponzone A Desnick RJ 《American journal of human genetics》2006,79(1):31-40
The classic phenotype of Fabry disease, X-linked alpha -galactosidase A (alpha -Gal A) deficiency, has an estimated incidence of approximately 1 in 50,000 males. The recent recognition of later-onset variants suggested that this treatable lysosomal disease is more frequent. To determine the disease incidence, we undertook newborn screening by assaying the alpha-Gal A activity in blood spots from 37,104 consecutive Italian male neonates. Enzyme-deficient infants were retested, and "doubly screened-positive" infants and their relatives were diagnostically confirmed by enzyme and mutation analyses. Twelve (0.03%) neonates had deficient alpha-Gal A activities and specific mutations, including four novel missense mutations (M51I, E66G, A73V, and R118C), three missense mutations (F113L, A143T, and N215S) identified previously in later-onset patients, and one splicing defect (IVS5(+1G-->T)) reported in a patient with the classic phenotype. Molecular modeling and in vitro overexpression of the missense mutations demonstrated structures and residual activities, which were rescued/enhanced by an alpha-Gal A-specific pharmacologic chaperone, consistent with mutations that cause the later-onset phenotype. Family studies revealed undiagnosed Fabry disease in affected individuals. In this population, the incidence of alpha-Gal A deficiency was 1 in approximately 3,100, with an 11 : 1 ratio of patients with the later-onset : classic phenotypes. If only known disease-causing mutations were included, the incidence would be 1 in approximately 4,600, with a 7 : 1 ratio of patients with the later-onset : classic phenotypes. These results suggest that the later-onset phenotype of Fabry disease is underdiagnosed among males with cardiac, cerebrovascular, and/or renal disease. Recognition of these patients would permit family screening and earlier therapeutic intervention. However, the higher incidence of the later-onset phenotype in patients raises ethical issues related to when screening should be performed--in the neonatal period or at early maturity, perhaps in conjunction with screening for other treatable adult-onset disorders. 相似文献
127.
Arivazhagan Rajendran Chunxia Zhao Burki Rajendar Viruthachalam Thiagarajan Yusuke Sato Seiichi Nishizawa Norio Teramae 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
We explain here the various non-covalent interactions which are responsible for the different binding modes of a small ligand with DNA.Methods
The combination of experimental and theoretical methods was used.Results
The interaction of amiloride with thymine was found to depend on the bases flanking the AP site and different binding modes were observed for different flanking bases. Molecular modeling, absorption studies and binding constant measurements support for the different binding patterns. The flanking base dependent recognition of AP site phosphates was investigated by 31P NMR experiments. The thermodynamics of the ligand–nucleotide interaction was demonstrated by isothermal titration calorimetry. The emission behavior of amiloride was found to depend on the bases flanking the AP site. Amiloride photophysics in the context of AP-site containing DNA is investigated by time-dependent density functional theory.Conclusions
Flanking bases affect the ground and excited electronic states of amiloride when binding to AP site, which causes flanking base-dependent fluorescence signaling.General significance
The various noncovalent interactions have been well characterized for the determination of nucleic acid structure and dynamics, and protein–DNA interactions. However, these are not clear for the DNA–small molecule interactions and we believe that our studies will bring a new insight into such phenomena. 相似文献128.
Somenath Bakshi Heejun Choi Nambirajan Rangarajan Kenneth J. Barns Benjamin P. Bratton James C. Weisshaar 《Applied and environmental microbiology》2014,80(16):4977-4986
Studies of time-dependent drug and environmental effects on single, live bacterial cells would benefit significantly from a permeable, nonperturbative, long-lived fluorescent stain specific to the nucleoids (chromosomal DNA). The ideal stain would not affect cell growth rate or nucleoid morphology and dynamics, even during laser illumination for hundreds of camera frames. In this study, time-dependent, single-cell fluorescence imaging with laser excitation and a sensitive electron-multiplying charge-coupled-device (EMCCD) camera critically tested the utility of “dead-cell stains” (SYTOX orange and SYTOX green) and “live-cell stains” (DRAQ5 and SYTO 61) and also 4′,6-diamidino-2-phenylindole (DAPI). Surprisingly, the dead-cell stains were nearly ideal for imaging live Escherichia coli, while the live-cell stains and DAPI caused nucleoid expansion and, in some cases, cell permeabilization and the halting of growth. SYTOX orange performed well for both the Gram-negative E. coli and the Gram-positive Bacillus subtilis. In an initial application, we used two-color fluorescence imaging to show that the antimicrobial peptide cecropin A destroyed nucleoid-ribosome segregation over 20 min after permeabilization of the E. coli cytoplasmic membrane, reminiscent of the long-term effects of the drug rifampin. In contrast, the human cathelicidin LL-37, while similar to cecropin A in structure, length, charge, and the ability to permeabilize bacterial membranes, had no observable effect on nucleoid-ribosome segregation. Possible underlying causes are suggested. 相似文献
129.
Raghuram Thiagarajan Amir Alavi Jagdeep T. Podichetty Jason N. Bazil Daniel A. Beard 《Algorithms for molecular biology : AMB》2017,12(1):8
Systems research spanning fields from biology to finance involves the identification of models to represent the underpinnings of complex systems. Formal approaches for data-driven identification of network interactions include statistical inference-based approaches and methods to identify dynamical systems models that are capable of fitting multivariate data. Availability of large data sets and so-called ‘big data’ applications in biology present great opportunities as well as major challenges for systems identification/reverse engineering applications. For example, both inverse identification and forward simulations of genome-scale gene regulatory network models pose compute-intensive problems. This issue is addressed here by combining the processing power of Graphics Processing Units (GPUs) and a parallel reverse engineering algorithm for inference of regulatory networks. It is shown that, given an appropriate data set, information on genome-scale networks (systems of 1000 or more state variables) can be inferred using a reverse-engineering algorithm in a matter of days on a small-scale modern GPU cluster. 相似文献