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81.
To understand how information flows and is used in the human brain, we must map neural structures at all levels, providing visualizations similar to those of Google Earth for continents, countries, cities, and streets. Unfortunately, the imaging and processing techniques currently used in connectomics projects cannot achieve complete mapping for the brains of large animals within the timespan of a typical research career. However, feasible improvements in x-ray imaging would change this situation. This Q&A discusses synchrotron x-ray tomography, an exciting new approach for in situ mapping of whole-brain wiring diagrams at multiple levels of spatial resolution. 相似文献
82.
Carolina V Morgante Patricia M Guimarães Andressa CQ Martins Ana CG Araújo Soraya CM Leal-Bertioli David J Bertioli Ana CM Brasileiro 《BMC research notes》2011,4(1):1-11
Background
Molecular genetic studies on rare tumour entities, such as bone tumours, often require the use of decalcified, formalin-fixed, paraffin-embedded tissue (dFFPE) samples. Regardless of which decalcification procedure is used, this introduces a vast breakdown of DNA that precludes the possibility of further molecular genetic testing. We set out to establish a robust protocol that would overcome these intrinsic hurdles for bone tumour research.Findings
The goal of our study was to establish a protocol, using a modified DNA isolation procedure and quality controls, to select decalcified samples suitable for array-CGH testing. Archival paraffin blocks were obtained from 9 different pathology departments throughout Europe, using different fixation, embedding and decalcification procedures, in order to preclude a bias for certain lab protocols. Isolated DNA samples were subjected to direct chemical labelling and enzymatic labelling systems and were hybridised on a high resolution oligonucleotide chip containing 44,000 reporter elements. Genomic alterations (gains and losses) were readily detected in most of the samples analysed. For example, both homozygous deletions of 0.6 Mb and high level of amplifications of 0.7 Mb were identified.Conclusions
We established a robust protocol for molecular genetic testing of dFFPE derived DNA, irrespective of fixation, decalcification or sample type used. This approach may greatly facilitate further genetic testing on rare tumour entities where archival decalcified, formalin fixed samples are the only source. 相似文献83.
Chia-Chi Chien Ivan M. Kempson Cheng Liang Wang H.H. Chen Yeukuang Hwu N.Y. Chen T.K. Lee Kelvin K.-C. Tsai Ming-Sheng Liu Kwang-Yu Chang C.S. Yang G. Margaritondo 《Biotechnology advances》2013
Complete profiling would substantially facilitate the fundamental understanding of tumor angiogenesis and of possible anti-angiogenesis cancer treatments. We developed an integrated synchrotron-based methodology with excellent performances: detection of very small vessels by high spatial resolution (~ 1 μm) and nanoparticle contrast enhancement, in vivo dynamics investigations with high temporal resolution (~ 1 ms), and three-dimensional quantitative morphology parametrization by computer tracing. The smallest (3–10 μm) microvessels were found to constitute > 80% of the tumor vasculature and exhibit many structural anomalies. Practical applications are presented, including vessel microanalysis in xenografted tumors, monitoring the effects of anti-angiogenetic agents and in vivo detection of tumor vascular rheological properties. 相似文献
84.
Jessica Ann Chacon Richard C. Wu Pariya Sukhumalchandra Jeffrey J. Molldrem Amod Sarnaik Shari Pilon-Thomas Jeffrey Weber Patrick Hwu Laszlo Radvanyi 《PloS one》2013,8(4)
Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) can induce tumor regression in up to 50% or more of patients with unresectable metastatic melanoma. However, current methods to expand melanoma TIL, especially the “rapid expansion protocol” (REP) were not designed to enhance the generation of optimal effector-memory CD8+ T cells for infusion. One approach to this problem is to manipulate specific co-stimulatory signaling pathways to enhance CD8+ effector-memory T-cell expansion. In this study, we determined the effects of activating the TNF-R family member 4-1BB/CD137, specifically induced in activated CD8+ T cells, on the yield, phenotype, and functional activity of expanded CD8+ T cells during the REP. We found that CD8+ TIL up-regulate 4-1BB expression early during the REP after initial TCR stimulation, but neither the PBMC feeder cells in the REP or the activated TIL expressed 4-1BB ligand. However, addition of an exogenous agonistic anti-4-1BB IgG4 (BMS 663513) to the REP significantly enhanced the frequency and total yield of CD8+ T cells as well as their maintenance of CD28 and increased their anti-tumor CTL activity. Gene expression analysis found an increase in bcl-2 and survivin expression induced by 4-1BB that was associated with an enhanced survival capability of CD8+ post-REP TIL when re-cultured in the absence or presence of cytokines. Our findings suggest that adding an agonistic anti-4-1BB antibody during the time of TIL REP initiation produces a CD8+ T cell population capable of improved effector function and survival. This may greatly improve TIL persistence and anti-tumor activity in vivo after adoptive transfer into patients. 相似文献
85.
Huai-Hsuan Tseng Sue-Huei Chen Chih-Min Liu Oliver Howes Yu-Lien Huang Ming H. Hsieh Chen-Chung Liu Jia-Chi Shan Yi-Ting Lin Hai-Gwo Hwu 《PloS one》2013,8(6)
Background
Patients with schizophrenia perform significantly worse on emotion recognition tasks than healthy participants across several sensory modalities. Emotion recognition abilities are correlated with the severity of clinical symptoms, particularly negative symptoms. However, the relationships between specific deficits of emotion recognition across sensory modalities and the presentation of psychotic symptoms remain unclear. The current study aims to explore how emotion recognition ability across modalities and neurocognitive function correlate with clusters of psychotic symptoms in patients with schizophrenia.Methods
111 participants who met the DSM-IV diagnostic criteria for schizophrenia and 70 healthy participants performed on a dual-modality emotion recognition task, the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and selected subscales of WAIS-III. Of all, 92 patients received neurocognitive evaluations, including CPT and WCST. These patients also received the PANSS for clinical evaluation of symptomatology.Results
The emotion recognition ability of patients with schizophrenia was significantly worse than healthy participants in both facial and vocal modalities, particularly fearful emotion. An inverse correlation was noted between PANSS total score and recognition accuracy for happy emotion. The difficulty of happy emotion recognition and earlier age of onset, together with the perseveration error in WCST predicted total PANSS score. Furthermore, accuracy of happy emotion and the age of onset were the only two significant predictors of delusion/hallucination. All the associations with happy emotion recognition primarily concerned happy prosody.Discussion
Deficits in emotional processing in specific categories, i.e. in happy emotion, together with deficit in executive function, may reflect dysfunction of brain systems underlying severity of psychotic symptoms, in particular the positive dimension. 相似文献86.
Objective
Myostatin and insulin-like growth factor 1 (IGF-1) are serum markers for muscle growth and regeneration. However, their value in the clinical monitoring of Pompe disease – a muscle glycogen storage disease – is not known. In order to evaluate their possible utility for disease monitoring, we assessed the levels of these serum markers in Pompe disease patients receiving enzyme replacement therapy (ERT).Design
A case-control study that included 10 patients with Pompe disease and 10 gender- and age-matched non-Pompe disease control subjects was performed in a referral medical center. Average follow-up duration after ERT for Pompe disease patients was 11.7 months (range: 6–23 months). Measurements of serum myostatin, IGF-1, and creatine kinase levels were obtained, and examinations of muscle pathology were undertaken before and after ERT in the patient group.Results
Compared with control subjects, Pompe disease patients prior to undergoing ERT had significantly lower serum IGF-1 levels (98.6 ng/ml vs. 307.9 ng/ml, p = 0.010) and lower myostatin levels that bordered on significance (1.38 ng/ml vs. 3.32 ng/ml, p = 0.075). After ERT, respective myostatin and IGF-1 levels in Pompe disease patients increased significantly by 129% (from 1.38 ng/ml to 3.16 ng/ml, p = 0.047) and 74% (from 98.6 ng/ml to 171.1 ng/ml, p = 0.013); these values fall within age-matched normal ranges. In contrast, myostatin and IGF-1 serum markers did not increase in age-matched controls. Follistatin, a control marker unrelated to muscle, increased in both Pompe disease patients and control subjects. At the same time, the percentage of muscle fibers containing intracytoplasmic vacuoles decreased from 80.0±26.4% to 31.6±45.3%.Conclusion
The increase in myostatin and IGF-1 levels in Pompe disease patients may reflect muscle regeneration after ERT. The role of these molecules as potential therapeutic biomarkers in Pompe disease and other neuromuscular diseases warrants further study. 相似文献87.
Background
Genomic selection is an appealing method to select purebreds for crossbred performance. In the case of crossbred records, single nucleotide polymorphism (SNP) effects can be estimated using an additive model or a breed-specific allele model. In most studies, additive gene action is assumed. However, dominance is the likely genetic basis of heterosis. Advantages of incorporating dominance in genomic selection were investigated in a two-way crossbreeding program for a trait with different magnitudes of dominance. Training was carried out only once in the simulation.Results
When the dominance variance and heterosis were large and overdominance was present, a dominance model including both additive and dominance SNP effects gave substantially greater cumulative response to selection than the additive model. Extra response was the result of an increase in heterosis but at a cost of reduced purebred performance. When the dominance variance and heterosis were realistic but with overdominance, the advantage of the dominance model decreased but was still significant. When overdominance was absent, the dominance model was slightly favored over the additive model, but the difference in response between the models increased as the number of quantitative trait loci increased. This reveals the importance of exploiting dominance even in the absence of overdominance. When there was no dominance, response to selection for the dominance model was as high as for the additive model, indicating robustness of the dominance model. The breed-specific allele model was inferior to the dominance model in all cases and to the additive model except when the dominance variance and heterosis were large and with overdominance. However, the advantage of the dominance model over the breed-specific allele model may decrease as differences in linkage disequilibrium between the breeds increase. Retraining is expected to reduce the advantage of the dominance model over the alternatives, because in general, the advantage becomes important only after five or six generations post-training.Conclusion
Under dominance and without retraining, genomic selection based on the dominance model is superior to the additive model and the breed-specific allele model to maximize crossbred performance through purebred selection. 相似文献88.
Li Y Efferson CL Ramesh R Peoples GE Hwu P Ioannides CG 《Cancer immunology, immunotherapy : CII》2011,60(4):515-524
Bacterial cell wall polysaccharides, such as PGN, bind and activate TLR-2, NOD2 and PGRP on monocytes/macrophages and activate
inflammation. We found that the peptides containing basic amino acids (cations) at N
-terminus and tyrosine at C-terminus interfered with activating ability of PGN. This finding is significant because the ECD
of TLR-2 in vivo encounters a large number of proteins or peptides. Some should bind ECD and “pre-form” TLR-2 to respond or
not to its activators, although they cannot activate TLR-2 alone. TLR-2 is receptor for a large number of ligands, including
lipopeptides and bacterial cell wall glycoproteins. A binding site for lipopeptides has been identified; however, a binding
site for soluble or multimeric PGN has not been proposed. To identify the candidate binding sites of peptides and PGN on TLR-2,
we modeled docking of peptides and of the PGN monomer (PGN-S-monomer) to extracellular domain (ECD-TLR-2) of the unbound TLR-2.
Quantification, in silico, of free energy of binding (DG) identified 2 close sites for peptides and PGN. The PGN-S-monomer
binding site is between amino acids TLR-2, 404–430 or more closely TLR-2, 417–428. The peptide-binding site is between amino
acids TLR-2, 434–455. Molecular models show PGN-S-monomer inserts its N
-acetyl-glucosamine (NAG) deep in the TLR-2 coil, while its terminal lysine interacts with inside (Glu403) and outside pocket (Tyr378). Peptides insert their two N
-terminal arginines or their C-terminal tyrosines in the TLR-2 coil. PGN did not bind the lipopeptide-binding site in the TLR-2.
It can bind the C-terminus, 572–586 (DG = 0.026 kcal), of “lipopeptide-bound” TLR-2. An additional, low-affinity PGN-binding
site is TLR-2 (227–237). MTP, MDP, and lysine-less PGN bind to TLR-2, 87–113. This is the first report identifying candidate
binding sites of monomer PGN and peptides on TLR-2. Experimental verification of our findings is needed to create synthetic
adjuvant for vaccines. Such synthetic PGN can direct both adjuvant and cancer antigen to TLR-2. 相似文献
89.
Hsiang-Chao Liu Ching-Shyung Hwu Chih-Jen Lu 《World journal of microbiology & biotechnology》2011,27(5):1071-1076
This study was focused on the effect of the presence of surfactant on the bioremediation efficacy and sensitivity of solid
phase microextraction (SPME) in the pyrene-contaminated soil. Soils with 1.3 and 7.6% soil organic matter (SOM) were tested
for biodegradation by microorganisms and extracted by aqueous solutions of the matrix used for SPME. For the biodegradation
test, the presence of Triton X-100 at 5× CMC (critical micelle concentration) significantly enhanced pyrene removal for soil
with lower SOM content (1.3%). However, this removal was insignificant for soil with higher SOM content (7.6%). The results
may suggest that 5× CMC was not sufficient to improve significantly pyrene desorption for soil with higher SOM content. For
the bioavailability test, in the absence of Triton X-100, SPME estimation of bioavailability in soils with indigenous or seeded
microorganisms had an error range within 15%. However, with addition of Triton X-100, SPME estimations showed a significant
decline (41 and 77%), in relation to their predicted values, for soil samples with SOM of 1.3 and 7.6%, respectively. The
main reason for this underestimation is that micelle formation from the application of surfactant impacted the concentration
of dissolved pyrene, rather than competitive site occupation between pyrene and surfactant molecules for SPME fiber. Thus,
if soil samples contain surfactant, SPME would significantly underestimate bioavailability and risk level of PAH-contaminated
sites. 相似文献
90.
The biomass yield of a continuous flow activated sludge system varied when the system treated influent containing different compositions of biogenic and xenobiotic substrates. Both the biogenic substrate and a test xenobiotic 2,4-dichlorophenoxyacetic acid (2,4-D) were degraded at steady-state activated sludge operations. The true yields, determined from steady-state activated sludge treatment performances, were at the maximum and the minimum when the activated sludge treated the influent of sole biogenic substrate and sole 2,4-D, respectively. The minimum yield was 56% of the maximum. Yield reduction between the maximum and the minimum was proportional to the concentration of 2,4-D in the influent. This trend of yield reduction suited a model that describes the metabolic uncoupling effect of 2,4-D on the sludge's degradation of the substrates. The model function variable was defined as the ratio of 2,4-D to biogenic COD concentrations in the influent. 相似文献