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Nadine Kretschmer Antje Hufner Christin Durchschein Katrin Popodi Beate Rinner Birgit Lohberger Rudolf Bauer 《International journal of molecular sciences》2021,22(5)
Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGloTM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma. 相似文献
3.
CPU虚拟化技术:单CPU模拟多CPU系统
我们在选购CPU的时候.对于这项CPU虚拟化技术的支持.通常并没不在意.因为这是我们日常应用所接触不到的环节,不过对于一些资深人员而言,虚拟化技术并不陌生。这项技术在传统的大型机和UNIX系统上早已普及,但因为桌面处理器大都使用的是X86架构,这决定了在其之上使用硬件级虚拟化技术的难度。 相似文献
4.
Horst Kesselmeier Inga Tschiersch Klaus Henning Beate Stoffels Sebastian Kutscha 《AI & Society》1998,12(1-2):55-63
Today technology design can no longer be understood as a design process on a green site. Design and implementation of new technology are always dependent on existing technology and the way it is used by people. In this respect Software-Engineering has also changed to the characteristics of normal technology design taking into account existing computer systems. Experiences show that the conditions and needs of such Software-Reengineering projects are highly complex and differ in their special characteristics ranging from aspects of quality of existing system documentation to organizational structures of the computer departments concerned. The Task-Artifact Cycle presented here gives a suitable reengineering approach emphasizing both analysis and design in Software-Reengineering. 相似文献
5.
Beate Grawemeyer 《Interacting with computers》2011,23(3):256-267
Security policies are required that protect information from unauthorised access, and also respect challenges users face in creating, and particularly managing, increasing numbers of passwords. This paper investigates real password use in the context of daily life. It presents the results of an empirical study where participants completed a password diary over 7 days, followed by debrief interviews to gain further knowledge and understanding of user behaviour. The results reported relate to how many passwords are in use, the types of passwords participants created, the relationships between different passwords and to sensitive services, how participants retrieved their passwords and finally, the different strategies adopted by users in their management of passwords. The paper concludes by providing a high level set of password guidelines, along with suggestions for mechanisms to support creating, encoding, retrieving and executing multiple passwords. 相似文献
6.
Daniel Alexander Bizjak Lucas John Lynn Matits Alisa Uhl Sebastian Victor Waldemar Schulz Jana Schellenberg Johannes Peifer Wilhelm Bloch Manfred Weiß Beate Grüner Hendrik Bracht Jürgen Michael Steinacker Marijke Grau 《International journal of molecular sciences》2022,23(23)
Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0–T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients. 相似文献
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8.
Bernhard Kienesberger Beate Obermüller Georg Singer Barbara Mittl Reingard Grabherr Sigrid Mayrhofer Stefan Heinl Vanessa Stadlbauer Angela Horvath Wolfram Miekisch Patricia Fuchs Ingeborg Klymiuk Holger Till Christoph Castellani 《International journal of molecular sciences》2021,22(12)
We aimed to assess the in vitro antimicrobial activity and the in vivo effect on the murine fecal microbiome and volatile organic compound (VOC) profile of (S)-reutericyclin. The antimicrobial activity of (S)-reutericyclin was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Staphylococcus (S.) epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa and Propionibacterium acnes. Reutericyclin or water were gavage fed to male BALBc mice for 7 weeks. Thereafter stool samples underwent 16S based microbiome analysis and VOC analysis by gas chromatography mass spectrometry (GC-MS). (S)-reutericyclin inhibited growth of S. epidermidis only. Oral (S)-reutericyclin treatment caused a trend towards reduced alpha diversity. Beta diversity was significantly influenced by reutericyclin. Linear discriminant analysis Effect Size (LEfSe) analysis showed an increase of Streptococcus and Muribaculum as well as a decrease of butyrate producing Ruminoclostridium, Roseburia and Eubacterium in the reutericyclin group. VOC analysis revealed significant increases of pentane and heptane and decreases of 2,3-butanedione and 2-heptanone in reutericyclin animals. The antimicrobial activity of (S)-reutericyclin differs from reports of (R)-reutericyclin with inhibitory effects on a multitude of Gram-positive bacteria reported in the literature. In vivo (S)-reutericyclin treatment led to a microbiome shift towards dysbiosis and distinct alterations of the fecal VOC profile. 相似文献
9.
When micropollutants degrade in the environment, they may form persistent and toxic transformation products, which should be accounted for in the environmental risk assessment of the parent compounds. Transformation products have become a topic of interest not only with regard to their formation in the environment, but also during advanced water treatment processes, where disinfection byproducts can form from benign precursors. In addition, environmental risk assessment of human and veterinary pharmaceuticals requires inclusion of human metabolites as most pharmaceuticals are not excreted into wastewater in their original form, but are extensively metabolized. All three areas have developed their independent approaches to assess the risk associated with transformation product formation including hazard identification, exposure assessment, hazard assessment including dose-response characterization, and risk characterization. This review provides an overview and defines a link among those areas, emphasizing commonalities and encouraging a common approach. We distinguish among approaches to assess transformation products of individual pollutants that are undergoing a particular transformation process, e.g., biotransformation or (photo)oxidation, and approaches with the goal of prioritizing transformation products in terms of their contribution to environmental risk. We classify existing approaches for transformation product assessment in degradation studies as exposure- or effect-driven. In the exposure-driven approach, transformation products are identified and quantified by chemical analysis followed by effect assessment. In the effect-driven approach, a reaction mixture undergoes toxicity testing. If the decrease in toxicity parallels the decrease of parent compound concentration, the transformation products are considered to be irrelevant, and only when toxicity increases or the decrease is not proportional to the parent compound concentration are the TPs identified. For prioritization of transformation products in terms of their contribution to overall environmental risk, we integrate existing research into a coherent model-based, risk-driven framework. In the proposed framework, read-across from data of the parent compound to the transformation products is emphasized, but limitations to this approach are also discussed. Most prominently, we demonstrate how effect data for parent compounds can be used in combination with analysis of toxicophore structures and bioconcentration potential to facilitate transformation product effect assessment. 相似文献
10.
Maria José Farré Sophie Day Peta A. Neale Daniel Stalter Janet Y.M. Tang Beate I. Escher 《Water research》2013
Disinfection by-products (DBP) formed from natural organic matter and disinfectants like chlorine and chloramine may cause adverse health effects. Here, we evaluate how the quantity and quality of natural organic matter and other precursors influence the formation of DBPs during chlorination and chloramination using a comprehensive approach including chemical analysis of regulated and emerging DBPs, total organic halogen quantification, organic matter characterisation and bioanalytical tools. In vitro bioassays allow us to assess the hazard potential of DBPs early in the chain of cellular events, when the DBPs react with their molecular target(s) and activate stress response and defence mechanisms. Given the reactive properties of known DBPs, a suite of bioassays targeting reactive modes of toxic action including genotoxicity and sensitive early warning endpoints such as protein damage and oxidative stress were evaluated in addition to cytotoxicity. Coagulated surface water was collected from three different drinking water treatment plants, along with reverse osmosis permeate from a desalination plant, and DBP formation potential was assessed after chlorination and chloramination. While effects were low or below the limit of detection before disinfection, the observed effects and DBP levels increased after disinfection and were generally higher after chlorination than after chloramination, indicating that chlorination forms higher concentrations of DBPs or more potent DBPs in the studied waters. Bacterial cytotoxicity, assessed using the bioluminescence inhibition assay, and induction of the oxidative stress response were the most sensitive endpoints, followed by genotoxicity. Source waters with higher dissolved organic carbon levels induced increased DBP formation and caused greater effects in the endpoints related to DNA damage repair, glutathione conjugation/protein damage and the Nrf2 oxidative stress response pathway after disinfection. Fractionation studies indicated that all molecular weight fractions of organic carbon contributed to the DBP formation potential, with the humic rich fractions forming the greatest amount of DBPs, while the low molecular weight fractions formed more brominated DBPs due to the high bromide to organic carbon ratio. The presence of higher bromide concentrations also led to a higher fraction of brominated DBPs as well as proportionally higher effects. This study demonstrates how a suite of analytical and bioanalytical tools can be used to effectively characterise the precursors and formation potential of DBPs. 相似文献