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1.
Renner S Ludwig V Boden O Scheffer U Göbel M Schneider G 《Chembiochem : a European journal of chemical biology》2005,6(6):1119-1125
TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules. 相似文献
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M. Shamim Hossain Sandro Hardy Atif Alamri Abdulhameed Alelaiwi Verena Hardy Christoph Wilhelm 《Multimedia Systems》2016,22(6):659-674
Stroke is considered one of the main causes of death around the world. Survivors often suffer different kinds of disabilities in terms of their cognitive and motor capabilities, and are therefore unable to perform their day-to-day activities. To regain some of their cognitive as well as motor abilities, they require rehabilitation. To this end, we present a serious game framework based on augmented reality technology that may motivate the patients’ involvement in the rehabilitation exercise. Additionally, we analyze the requirements for such a framework and describe the concept and implementation of the proposed approach. Furthermore, we designed a wireless vibrotactile output device that is attached to a tangible object. The tangible object that is connected to the framework can give haptic as well as audio-visual feedback to the patient in a more motivating and entertaining environment for rehabilitation exercises. The suitability and utility of the proposed framework was evaluated with real stroke patients and compared against the performance of a healthy control group, thus facilitating occupational therapists in assessing a patient’s progress. Our evaluations show that the serious games with vibrotactile feedback are well accepted by patients. 相似文献
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Werner Heimann und Verena Klaiber 《Zeitschrift für Lebensmitteluntersuchung und -Forschung A》1977,165(3):131-136
Zusammenfassung Die Untersuchung einer aus Roggen gewonnenen Lipoxygenase-aktiven Enzymfraktion ergab, daß Roggenlipoxygenase ein Molekulargewicht von ca. 102000 besitzt. Bei der isoelektrischen Fokussierung traten zwei Bandengruppen mit isoelektrischen Punkten zwischen 5,1–5,5 und 5,8–6,4 auf. Durch Ionenaustauschchromatographie konnten drei Isoenzyme gewonnen werden. Das pH-Optimum der Umsetzung lag bei 7,3–7,5. Roggenlipoxygenase katalysiert vorwiegend die Bildung von 13-Hydroperoxy-9-cis,11-trans-octadecadiensäure (13-LHPO). Durch eine hochmolekulare Proteinfraktion wurden in Roggen die LHPO zu a-Ketolen umgesetzt. Diese Roggenisomerase setzt die von der systemeigenen Lipoxygenase gebildeten LHPO zu überwiegend 12,13-Ketohydroxysduren um. Roggenisomerase hat eine Michaeliskonstante von 3–5 × 10–5, (LHPO). Die Reaktionsgeschwindigkeit der Umsetzung stieg bei kleinen Proteinkonzentrationen linear mit der Proteinkonzentration.
On lipoxygenase and enzymes which decompose linoleic acid hydroperoxides in rye
Summary An enzyme fraction from rye containing lipoxygenase activity was investigated. The molecular weight of lipoxygenase was found to be about 102000. Two bands groups with isoelectric points between 5.1–5.5 and 5.8–6.4 were obtained by isoelectric focusing. Three isoenzymes could be separated by ion exchange chromatography. Lipoxygenase has optimum activity at pH 7.3–7.5 and predominantly forms 13-hydroperoxy-9-cis,11-trans-octadecadienoic acid (13-LHPO).In rye the 13-LHPO is converted to -ketols by a high molecular protein fraction. This isomerase converts the LHPO formed by rye lipoxygenase predominantly to 12,13-ketohydroxy acids. The Michaelis Constant of isomerase is 3–5 × 10–5, using LHPO as substrate. At low protein concentrations the reaction velocity of LHPO-conversion increases linearly with protein concentration.相似文献
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Verena Moosbrugger-Martinz Corinne Leprince Marie-Claire Mchin Michel Simon Stefan Blunder Robert Gruber Sandrine Dubrac 《International journal of molecular sciences》2022,23(10)
The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin. 相似文献
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Petra Pavel Stefan Blunder Verena Moosbrugger-Martinz Peter M. Elias Sandrine Dubrac 《International journal of molecular sciences》2022,23(4)
Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease in which dry and itchy skin may develop into skin lesions. AD has a strong genetic component, as children from parents with AD have a two-fold increased chance of developing the disease. Genetic risk loci and epigenetic modifications reported in AD mainly locate to genes involved in the immune response and epidermal barrier function. However, AD pathogenesis cannot be fully explained by (epi)genetic factors since environmental triggers such as stress, pollution, microbiota, climate, and allergens also play a crucial role. Alterations of the epidermal barrier in AD, observed at all stages of the disease and which precede the development of overt skin inflammation, manifest as: dry skin; epidermal ultrastructural abnormalities, notably anomalies of the lamellar body cargo system; and abnormal epidermal lipid composition, including shorter fatty acid moieties in several lipid classes, such as ceramides and free fatty acids. Thus, a compelling question is whether AD is primarily a lipid disorder evolving into a chronic inflammatory disease due to genetic susceptibility loci in immunogenic genes. In this review, we focus on lipid abnormalities observed in the epidermis and blood of AD patients and evaluate their primary role in eliciting an inflammatory response. 相似文献
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Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The standard of care in medically and physically fit patients is intensive induction therapy. The majority of these intensively treated patients achieve a complete remission. However, a high number of these patients will experience relapse. In patients older than 60 years, the results are even worse. Therefore, new therapeutic approaches are desperately needed. One promising approach in high-risk leukemia to prevent relapse is the induction of the immune system simultaneously or after reduction of the initial tumor burden. Different immunotherapeutic approaches such as allogenic stem cell transplantation or donor lymphocyte infusions are already standard therapies, but other options for AML treatment are in the pipeline. Moreover, the therapeutic landscape in AML is rapidly changing, and in the last years, a number of immunogenic targets structures eligible for specific therapy, risk assessment or evaluation of disease course were determined. For example, leukemia-associated antigens (LAA) showed to be critical as biomarkers of disease state and survival, as well as markers of minimal residual disease (MRD). Yet many mechanisms and properties are still insufficiently understood, which also represents a great potential for this form of therapy. Therefore, targeted therapy as immunotherapy could turn into an efficient tool to clear residual disease, improve the outcome of AML patients and reduce the relapse risk. In this review, established but also emerging immunotherapeutic approaches for AML patients will be discussed. 相似文献