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排序方式: 共有321条查询结果,搜索用时 62 毫秒
1.
Dr. Emilianne M. Limbrick Audrey E. Yñigez-Gutierrez Callie C. Dulin Dagmara K. Derewacz Dr. Jeffrey M. Spraggins Dr. Kathryn M. McCulloch Prof. T. M. Iverson Prof. Brian O. Bachmann 《Chembiochem : a European journal of chemical biology》2020,21(23):3349-3358
Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A1, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A1- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A1-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates. 相似文献
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Malgorzata Kloc Ahmed Uosef Jacek Z. Kubiak Rafik Mark Ghobrial 《International journal of molecular sciences》2021,22(1)
The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages and the components of the RhoA pathway are attractive targets for anti-atherosclerotic therapies, which would inhibit macrophage influx and inflammatory phenotype, maintain an anti-inflammatory environment, and promote tissue remodeling and repair. Here, we discuss the recent findings on the role of macrophages and RhoA pathway in the atherosclerotic plaque formation and resolution and the novel therapeutic approaches. 相似文献
4.
Dawid Polak Marcin Talar Nina Wolska Dagmara W. Wojkowska Kamil Karolczak Karol Kramkowski Tomasz A. Bonda Cezary Watala Tomasz Przygodzki 《International journal of molecular sciences》2021,22(6)
Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y12 could serve as components of dual anti-platelet therapy. We have found that a selective A2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y12 inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146. 相似文献
5.
Malgorzata Plaza 《Information Systems Frontiers》2008,10(3):347-359
Although the Earned Value Method (EVM), a multi-dimensional project control system, has been widely used since 1960, there
has been little research focused specifically on its application in IS implementation. The management of IS projects—including
the accurate forecasting of project duration—is complicated by the strong impact of the learning curve on the effectiveness
of EVM. This study makes new contributions by advancing formulas for the accurate prediction of project duration, and by developing
a decision support model in which the learning curve is fully integrated with EVM, and performance changes due to learning
are isolated from other factors affecting project duration. The study makes three contributions to the understanding and use
of EVM in IS implementation: (1) It provides an extended version of EVM, (2) it provides an illustration of the application
of EVM to a real project situation based on empirical data from an ERP implementation project, and (3) it provides a theoretical
basis for empirical studies of IS project control techniques. The decision support model can be used to determine both the
learning curve coefficient and the project completion date during the early stages of a project, and it thus offers a significant
practical contribution to the management of IS projects.
Dr. Margaret Plaza is an Associate Professor of Information Technology Management at Ryerson University and a Senior Research Scientist in IITM. She holds an M.Sc. in Mechanical Engineering and a Ph.D. in Production Engineering from Politechnika Krakowska (Cracow University of Technology) where she specialized in flexible manufacturing systems. Dr. Plaza is also a PEng. (Ontario), PMP, and CIA and has over 20 years’ industry experience working with consulting and manufacturing firms in both private and public sectors. She managed or provided consulting for ERP and supply chain implementations. Her current research focuses on organizational learning, technology management and the supply chain. She has developed decision models and decision support technologies to assist managers with problems in new technology implementations. 相似文献
Malgorzata PlazaEmail: |
Dr. Margaret Plaza is an Associate Professor of Information Technology Management at Ryerson University and a Senior Research Scientist in IITM. She holds an M.Sc. in Mechanical Engineering and a Ph.D. in Production Engineering from Politechnika Krakowska (Cracow University of Technology) where she specialized in flexible manufacturing systems. Dr. Plaza is also a PEng. (Ontario), PMP, and CIA and has over 20 years’ industry experience working with consulting and manufacturing firms in both private and public sectors. She managed or provided consulting for ERP and supply chain implementations. Her current research focuses on organizational learning, technology management and the supply chain. She has developed decision models and decision support technologies to assist managers with problems in new technology implementations. 相似文献
6.
Viscosity is one of the most important attributes of rye-based products related to some health benefits. To identify the factors affecting arabinoxylan-dependent extract viscosity (AX-EV) of rye bread, the structural features of water-extractable arabinoxylans (WE-AXs) and their ammonium sulphate precipitated subfractions were investigated in breads with varied viscosities. Also, an endoxylanase activity in the starting flours was examined. The HPSEC-RI profiles revealed the higher extent of AX depolymerisation in whole-meal bread (WMB) when compared to that in endosperm bread (EB), resulting in its lower AX-EV. This was mostly related to lower molecular weight of the parent WE-AX fraction with distinctly lower proportion of 2-Xylp in the chain. The AX-EV of rye bread decreased with decreasing proportion of AX-I, the major subfraction with 3-Xylp as only branching site. The endoxylanase activity was at least two times lower in endosperm flour than that in WM and negatively correlated with the AX-EV of WMB. The importance of densely substituted AX subfractions with exclusively 2-Xylp and 2,3-Xylp branches, protecting the AX-I from enzymic degradation during bread-making, has been evidenced. 相似文献
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8.
Synthesis of trimethylene carbonate/ϵ‐caprolactone copolymers initiated with zinc alkoxide: influence of copolymer chain microstructure on thermal and mechanical properties
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Malgorzata Pastusiak Piotr Dobrzynski Janusz Kasperczyk Michal Sobota Bozena Kaczmarczyk Henryk Janeczek 《Polymer International》2017,66(9):1259-1268
Ethylzinc(II ) ethoxide is a highly active and efficient initiator for the bulk polymerization of 1,3‐trimethylene carbonate and its copolymerization with ? ‐caprolactone. This initiator allows one to obtain (co)polymers with high molar masses in quite a short time. Significant difference in co‐monomer reactivity and relatively low participation of intermolecular transesterification processes lead to the obtained copolymers being characterized by a gradient chain microstructure. In 13C NMR spectra, in all regions, we observed the presence of triads which were distinctly represented by four peaks for the carbonyl signal. Mechanical tests showed that copolymers containing 70% and more of ? ‐caprolactone presented a relatively high Young's modulus and a very high maximum elongation factor; therefore these materials are promising in many biomedical applications. Due to the high reaction rate, we also made an attempt at copolymerization using reactive extrusion which gave promising results. © 2017 Society of Chemical Industry 相似文献
9.
Malgorzata Młynarczyk Malgorzata Sznitowska Dorota Watrobska-Swietlikowska 《Drug development and industrial pharmacy》2013,39(4):355-362
Antimicrobial efficacy of methyl and propylparaben combination as potential preservatives for submicron emulsions, and the effect of oil and lecithin concentration on the microbial growth were investigated. Parabens were ineffective in standard or doubled concentrations as per pharmacopoeial criteria. Poor growth inhibition and multiplication of reference strains point to protective and growth properties of submicron emulsions. No correlation was observed between oil/lecithin ratio and efficacy of parabens; partitioning of the latter into the oily phase and lipophilic domains could be the reason for such effect. Further studies are necessary to establish a stable and safe composition of such formulations. 相似文献
10.
Renata Rybakiewicz David Djurado Hubert Cybulski Ewelina Dobrzynska Irena Kulszewicz-Bajer Damien Boudinet Jean-Marie Verilhac Malgorzata Zagorska Adam Pron 《Synthetic Metals》2011,161(15-16):1600-1610
New solution processable organic semiconductors, consisting of pyrromelitic, naphthalene or perylene bisimide core and triarylamine N-substituents, have been synthesized. All three compounds are electrochemically active and undergo quasi-reversible oxidation and reduction as evidenced by cyclic voltammetry investigations. The oxidation process involves the transformation of the triarylamine substituents into radical cations as proven spectroscopically and spectroelectrochemically. The reduction process occurs at the arylene bisimide core leading to the formation of a radical anion and eventually a dianion in the second step. These findings are in perfect agreement with the DFT calculations which show that in the synthesized molecules the HOMO orbital is located on the triarylamine moiety whereas the LUMO one on the bisimide core. In all molecules studied the electrochemically determined ionization potential (IP) is slightly higher than 5.0 eV whereas in naphthalene and perylene derivatives the electron affinity (EA) is close to ?3.9 eV. These values fulfill the requirements for n-type (electron) semiconductors in air operating n-channel field effect transistors (FETs) as well as for p-type (hole) conductors in p-channel FETs. To verify whether the newly synthesized compounds exhibit the expected electrical transport properties all organic (CYTOP dielectric) test transistors were fabricated. All three semiconductors showed no field effect in the n-channel configuration. To the contrary, they could be used in p-channel FETs showing, in the saturation regime, the hole mobility approaching 10?4 cm2 V?1 s?1 – the value which slightly exceeds that measured for low molecular weight, amorphous triarylamine semiconductors. 相似文献