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41.
    
The chemical milieu, microbiota composition, and immune activity show prominent differences in distinct healthy skin areas. The objective of the current study was to compare the major permeability barrier components (stratum corneum and tight junction (TJ)), investigate the distribution of (corneo)desmosomes and TJs, and measure barrier function in healthy sebaceous gland-rich (SGR), apocrine gland-rich (AGR), and gland-poor (GP) skin regions. Molecules involved in cornified envelope (CE) formation, desquamation, and (corneo)desmosome and TJ organization were investigated at the mRNA and protein levels using qRT-PCR and immunohistochemistry. The distribution of junction structures was visualized using confocal microscopy. Transepidermal water loss (TEWL) functional measurements were also performed. CE intracellular structural components were similarly expressed in gland-rich (SGR and AGR) and GP areas. In contrast, significantly lower extracellular protein levels of (corneo)desmosomes (DSG1 and CDSN) and TJs (OCLN and CLDN1) were detected in SGR/AGR areas compared to GP areas. In parallel, kallikrein proteases were significantly higher in gland-rich regions. Moreover, gland-rich areas were characterized by prominently disorganized junction structures ((corneo)desmosomes and TJs) and significantly higher TEWL levels compared to GP skin, which exhibited a regular distribution of junction structures. According to our findings, the permeability barrier of our skin is not uniform. Gland-rich areas are characterized by weaker permeability barrier features compared with GP regions. These findings have important clinical relevance and may explain the preferred localization of acantholytic skin diseases on gland-rich skin regions (e.g., Pemphigus foliaceus, Darier’s disease, and Hailey–Hailey disease).  相似文献   
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Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η5-C5Me5)(H2O)3]2+ and [Ru(η6-p-cymene)(H2O)3]2+ ions by pH-potentiometry, UV-visible spectrophotometry and 1H NMR spectroscopy. Due to the zwitterionic structure of the ligands, they possess excellent water solubility as well as their complexes. The complexes exhibit high solution stability in a wide pH range; no significant dissociation occurs at physiological pH. The hybrids and their Rh(η5-C5Me5) complexes displayed enhanced cytotoxicity in human colon adenocarcinoma cell lines and exhibited multidrug resistance selectivity. In addition, the Rh(η5-C5Me5) complexes showed increased selectivity to the chemosensitive cancer cells over the normal cells; meanwhile, the Ru(η6-p-cymene) complexes were inactive, most likely due to arene loss. Interaction of the complexes with human serum albumin (HSA) and calf-thymus DNA (ct-DNA) was investigated by capillary electrophoresis, fluorometry and circular dichroism. The complexes are able to bind strongly to HSA and ct-DNA, but DNA cleavage was not observed. Changing the five-membered proline ring to the six-membered homoproline resulted in increased lipophilicity and cytotoxicity of the Rh(η5-C5Me5) complexes while changing the configuration (L vs. D) rather has an impact on HSA or ct-DNA binding.  相似文献   
43.

Definition of the problem

Fifteen years after establishing neuroethics as an international academic field, neuroethics has emerged as a vibrant, dynamic area of scientific research.

Arguments

Within a short period of a few years, specific conferences, journals, research funding programs, professional societies, and institutes were founded. Nonetheless, considerable disagreement about its definition and subject matter still remain. We argue for a differentiated conceptualization according to which the deliberate reflection of ethical problems arising from the neurosciences and their predominantly neurotechnological application belongs as much to neuroethics as does the ethical reflection of the neuroscience of morality. This does not comprise neuroscientific or neuropsychological research on morality itself, but includes the contemplation of the significance of such research for ethics and the law. Here, we provide an overview about the most important topics in neuroethics and elucidate the relevance of neuroethics for a vast diversity of societal domains reaching well beyond medicine and health care.

Conclusion

The great potential of neuroethics as a novel branch of academic research lies in finding new answers to pressing questions of high societal relevance by linking neurophilosophy and bioethics topics as well as its broad interdisciplinary network.
  相似文献   
44.
Multi-walled carbon nanotube (MWCNT) reinforced silicon nitride composites have been prepared by hot isostatic pressing at 20 MPa and gas pressure sintering at 2 MPa. To assure a good dispersion of the MWCNTs a highly efficient attritor milling was employed in the preparation process of the powder mixtures. The morphological and micro-structural evolution of the powder particles during the high-energy milling was monitored.We have found that the milling time has a complex influence on the structure and mechanical properties of the resulting nanocomposites through affecting both the dispersion and degradation of the nanoscale filler as well as the phase transformations of the ceramic host.  相似文献   
45.
The adsorption of water vapour in a high surface area commercial carbon, as-received and after different surface chemical treatments was investigated as a function of relative humidity by three separate techniques. While gravimetry and small and wide angle X-ray scattering measurements are in reasonable agreement, volumetric observations yielded isotherms with substantially lower values for the water uptake. In each case, the results are sensitive to the surface chemistry of the sample. Several weeks were required to establish equilibrium, with strikingly different results being obtained for measurements carried out on shorter time scales. The slow kinetics of the uptake accounts for most of the discrepancies among the results of the different techniques. Immersion in water caused significant macroscopic swelling of the carbon matrix over a time scale comparable to the adsorption equilibrium time.  相似文献   
46.
    
(1) Adeno-associated viruses (AAV) are safe and efficient gene therapy vectors with promising results in the treatment of several diseases. Extracellular vesicles (EV) are phospholipid bilayer-surrounded structures carrying several types of lipids, proteins, and nucleic acids with the ability to cross biological barriers. EV-associated AAVs might serve as new and efficient gene therapy vectors considering that they carry the benefits of both AAVs and EVs. (2) We tested vesicle-associated AAVs and vesicles mixed with AAVs on two major cell types of the central nervous system: a neural cell line (N2A) and primary astrocyte cells. (3) In contrast to previously published in vivo observations, the extracellular vesicle packaging did not improve but, in the case of primary astrocyte cells, even inhibited the infection capacity of the AAV particles. The observed effect was not due to the inhibitory effects of the vesicles themselves, since mixing the AAVs with extracellular vesicles did not change the effectiveness. (4) Our results suggest that improvement of the in vivo efficacy of the EV-associated AAV particles is not due to the enhanced interaction between the AAV and the target cells, but most likely to the improved delivery of the AAVs through tissue barriers and to the shielding of AAVs from neutralizing antibodies.  相似文献   
47.
Typical atrial flutter is a macro-reentrant arrhythmia within the right atrium. Its zone of slow conduction is the so-called right atrial isthmus, representing the area between inferior vena cava, tricuspid annulus, and coronary sinus. Conduction block of this target area can terminate the arrhythmia and prevent reinduction. Isthmus ablation with radiofrequency (RF) energy is a well-established technique to produce conduction block. However, in most cases multiple energy applications are needed to create linear lesions. In individual cases, this results in prolonged procedure duration and, as a possible result of nontransmural lesions, recurrence of the arrhythmia. This article evaluates the feasibility and safety of a new steerable temperature-monitoring microwave ablation catheter in the production of linear lesions in the right atrial isthmus and examines both the dose-response relationship and the energy required for transmural lesions. Ablation was performed in eight open-chest mongrel dogs using a 2.450-MHz microwave generator with 35-50 W and a newly designed AFx 9-F deflectable catheter with a 25-mm antenna on the tip. The operation was performed under general anesthesia using nembutal and supported with room-air artificial respiration throughout the procedure. The study showed that the new deflectable AFx microwave catheter is a feasible and safe tool for creating long transmural linear lesions in the right isthmus. Based on this data, an appropriate catheter position, energy settings between 40 and 50 W, and application duration of approximately 90 s are needed. Also, the development of different antennas and curve shapes is recommended to simplify the ablation procedure and to target more complex arrhythmia substrates with microwave energy. Further studies are needed to determine the optimal anticoagulation procedure after microwave ablation.  相似文献   
48.
Bio‐orthogonal labelling schemes based on inverse‐electron‐demand Diels–Alder (IEDDA) cycloaddition have attracted much attention in chemical biology recently. The appealing features of this reaction, such as the fast reaction kinetics, fully bio‐orthogonal nature and high selectivity, have helped chemical biologists gain deeper understanding of biochemical processes at the molecular level. Listing the components and discussing the possibilities and limitations of these reagents, we provide a recent snapshot of the field of IEDDA‐based biomolecular manipulation with special focus on fluorescent modulation approaches through the use of bio‐orthogonalized building blocks. At the end, we discuss challenges that need to be addressed for further developments in order to overcome recent limitations and to enable researchers to answer biomolecular questions in more detail.  相似文献   
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