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91.
Agent-Based Modeling and Simulation (ABMS) has arisen as new approach to effectively support domain experts to cope with the growing complexity of the problems which they have to face and solve. To date, few methodologies are available which can be exploited by domain experts with limited programming expertise to model and subsequently analyze complex systems typical of their application domains. In this paper the easyABMS methodology is proposed to overcome the lack of integrated methodologies able to seamlessly guide domain experts from the analysis of the system under consideration to its modeling and analysis of simulation results. The effectiveness of easyABMS is also experimented through a case study in the logistics domain which concerns the analysis of different policies for managing vehicles used for stacking and moving containers in a transhipment terminal. 相似文献
92.
Dr. Richard J. B. H. N. van den Berg Dr. Erwin R. van Rijssel Maria Joao Ferraz Judith Houben Anneke Strijland Wilma E. Donker‐Koopman Dr. Tom Wennekes Dr. Kimberly M. Bonger Dr. Amar B. T. Ghisaidoobe Dr. Sascha Hoogendoorn Prof. Dr. Gijsbert A. van der Marel Dr. Jeroen D. C. Codée Prof. Dr. Herman S. Overkleeft Prof. Dr. Johannes M. F. G. Aerts 《ChemMedChem》2015,10(12):2042-2062
Glucosylceramide metabolism and the enzymes involved have attracted significant interest in medicinal chemistry, because aberrations in the levels of glycolipids that are derived from glucosylceramide are causative in a range of human diseases including lysosomal storage disorders, type 2 diabetes, and neurodegenerative diseases. Selective modulation of one of the glycoprocessing enzymes involved in glucosylceramide metabolism—glucosylceramide synthase (GCS), acid glucosylceramidase (GBA1), or neutral glucosylceramidase (GBA2)—is therefore an attractive research objective. In this study we took two established GCS inhibitors, one based on deoxynojirimycin and the other a ceramide analogue, and merged characteristic features to obtain hybrid compounds. The resulting 39‐compound library does not contain new GCS inhibitors; however, a potent (200 nm ) GBA1 inhibitor was identified that has little activity toward GBA2 and might therefore serve as a lead for further biomedical development as a selective GBA1 modulator. 相似文献
93.
Karnda Sengloyluan Kannika Sahakaro Wilma K.Dierkes Jacques W.M.Noordermeer 肖大玲摘译 《轮胎工业》2014,34(6):359-367
正白炭黑和炭黑为广泛用于橡胶中的补强填料。由于白炭黑和炭黑表面特征不相同,它们虽然都容易形成聚集体,但形成聚集体的原因却不相同,导致它们的分散能力不相同。炭黑-炭黑相互作用主要是由范德华作用力引起的,其在混炼过程中容易被破坏。白炭黑聚集体是由氢键、范德华作用力和其他物理作用力共同作用形成的更强的填料-填料相互作用。白炭黑表面的硅烷醇 相似文献
94.
Massimiliano Marziale Wilma Polini 《The International Journal of Advanced Manufacturing Technology》2009,43(11-12):1106-1123
Mechanical products are usually made by assembling many parts. The dimensional and geometrical variations of each part have to be limited by tolerances able to ensure both a standardized production and a certain level of quality, which is defined by satisfying functional requirements. The appropriate allocation of tolerances among the different parts of an assembly is the fundamental tool to ensure assemblies that work rightly at lower costs. Therefore, there is a strong need to develop a tolerance analysis to satisfy the requirements of the assembly by the tolerances imposed on the single parts. This tool has to be based on a mathematical model able to evaluate the cumulative effect of the single tolerances. Actually, there are some different models used or proposed by the literature to make the tolerance analysis of an assembly, but none of them is completely and univocally accepted. Some authors focus their attention on the solution of single problems found in these models or in their practical application in computer-aided tolerancing systems. But none of them has done an objective and complete comparison among them, analyzing the advantages and the weakness and furnishing a criterion for their choice and application. This paper briefly introduces two of the main models for tolerance analysis, the vector loop and the matrix. In this paper, these models are briefly described and then compared showing their analogies and differences. 相似文献
95.
Antonio Buzharevski Dr. Svetlana Paskas Dr. Menyhárt-Botond Sárosi Dr. Markus Laube Dr. Peter Lönnecke Dr. Wilma Neumann Dr. Sanja Mijatovic Dr. Danijela Maksimovic-Ivanic Prof. Dr. Jens Pietzsch Prof. Dr. Dr. h.c. mult. Evamarie Hey-Hawkins 《ChemMedChem》2019,14(3):315-321
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common way of treating inflammatory disorders. Their widespread use helped reveal their other modes of action as pharmaceuticals, such as a profound effect on various cancers. Celecoxib has proven to be a very prominent member of this group with cytostatic activities. On the other hand, the highly dynamic field of drug design is constantly searching for new ways of modifying known structures to obtain more powerful and less harmful drugs. A very interesting development is the implementation of carboranes in pharmacologically active structures, mostly as phenyl mimetics. Herein we report the synthesis of three carborane-containing derivatives of the COX-2-selective NSAID celecoxib. The new compounds proved to have promising cytostatic potential against various melanoma and colorectal adenocarcinoma cell lines. Inhibited proliferation accompanied by caspase-independent apoptotic cell death was found to be the main cause of decreased cell viability upon treatment with the most efficient celecoxib analogue, 3 b (4-[5-(1,7-dicarba-closo-dodecaboranyl)-3-trifluoromethyl-1H-pyrazol-1-yl]-1-methylsulfonylbenzene). 相似文献
96.
Hospital wastewater has been described as an important source of spreading pathogenic microorganisms in the environment. However, there are few studies reporting the presence and concentrations of gastroenteric viruses and hepatitis A viruses in these environmental matrices. The aim of this study was to assess the contamination by viruses responsible for acute gastroenteritis and hepatitis derived from hospital wastewater treatment plants (WWTPs). Rotavirus A (RV-A), human adenoviruses (HAdV), norovirus genogroup I and II (NoV GI/GII) and hepatitis A viruses (HAV) were detected and quantified in sewage samples from two WWTPs located in Rio de Janeiro (Brazil) that operates different sewage treatments. WWTP-1 uses an Upflow Anaerobic Sludge Blanket (UASB reactor) and three serial anaerobic filters while WWTP-2 uses aerobic processes, activated sludge with extended aeration and final chlorination of the effluents. Viruses’ detection was investigated by using conventional PCR/RT-PCR, quantitative real-time PCR (qPCR) and partial sequencing of the genome of the viruses detected. Rate of viruses detection ranged from 7% (NoV GI in WWTP-1) to 95% (RV-A in WWTP-2) and genome from all viruses were detected. The most prevalent genotypes were RV-A SG I, HAdV species D and F, NoV GII/4 and HAV subgenotype IA. Mean values of viral loads (genome copies (GC)/ml) obtained in filtered effluents from anaerobic process was 1.9 × 103 (RV-A), 2.8 × 103 (HAdV) and 2.4 × 103 (NoV GII). For chlorinated effluents from activated sludge process, the mean values of viral loads (GC/ml) was 1.2 × 105 (RV-A), 1.4 × 103 (HAdV), 8.1 × 102 (NoV GII) and 2.8 × 104 (HAV). Data on viral detection in treated effluents of hospital WWTPs confirmed the potential for environmental contamination by viruses and could be useful to establish standards for policies on wastewater management. 相似文献
97.
Dieuwertje E. Kok Wilma T. Steegenga Eddy J. Smid Erwin G. Zoetendal Cornelia M. Ulrich Ellen Kampman 《Critical reviews in food science and nutrition》2020,60(2):244-256
AbstractFolate is a B-vitamin with an important role in health and disease. The optimal folate status with regard to human health remains controversial. A low intake of natural folate as well as excessive intake of synthetic folic acid, were previously linked to an increased risk of colorectal cancer or with aberrant molecular pathways related to carcinogenesis in some studies. Importantly, most studies conducted so far, solely focused on dietary intake or circulating levels of folate in relation to cancer risk. Notably, diet or dietary supplements are not the only sources of folate. Several bacteria in the gastrointestinal tract can synthesize B-vitamins, including folate, in quantities that resemble dietary intake. The impact of bacterial folate biosynthesis concerning human health and disease remains unexplored. This review highlights current insights into folate biosynthesis by intestinal bacteria and its implications for processes relevant to cancer development, such as epigenetic DNA modifications and DNA synthesis. Moreover, we will reflect on the emerging question whether food-grade or intestinal bacteria can be considered a potential target to ensure sufficient levels of folate in the gastrointestinal tract and, hence the relevance of bacterial folate biosynthesis for disease prevention or treatment. 相似文献
98.
Zegers BN Lewis WE Booij K Smittenberg RH Boer W de Boer J Boon JP 《Environmental science & technology》2003,37(17):3803-3807
The levels of 14 brominated diphenyl ether (BDE)-congeners in sediment cores from three locations in Western Europe have been determined by GC/MS (negative chemical ionization mode). Sediments from the Drammenfjord (Norway), the western Wadden Sea (The Netherlands), and the freshwater Lake Woserin (Mecklenburg-Vorpommern, Germany) showed a time-dependent pattern in the distribution of BDEs since the beginning of the industrial production of polybrominated diphenyl ether (PBDE) formulations. Two out of three commercially available PBDE formulations could be distinguished. Starting from the beginning of the 1970s, the penta-mix formulation is clearly present, but the deca-mix formulation is only present since the late 1970s. The octa-mix formulation appeared to be still absent in these sediments, as its marker-congener, BDE183, was never detected. In the cores from the western Wadden Sea and Lake Woserin, all TOC-normalized concentrations of the penta-BDE-derived congeners were leveling off in the most recent sediment layers representing 1995 and 1997, whereas those in the Drammenfjord were still increasing in 1999. The levels of BDE209, however, decreased in the most recent layer of all three cores. In Lake Woserin, the concentrations of BDE209 were much less elevated above those of the tri- to hexa-BDEs than in the other the two areas. This might be due to the absence of a significant PBDE input from sources other than the atmosphere to this rural lake. The absence of all PBDE congeners in the older layers of the three sediment cores, as well as in several 100-150-My-old layers from an extremely organic-rich marine sediment from the Kimmeridge clay formation in Dorset (UK), indicated the absence of natural production of the BDE congeners analyzed. 相似文献
99.
Anxiety about separation from a child is highly salient to parents and, when studied in mothers, has been shown to relate to important personality attributes. This longitudinal study examined origins of separation anxiety, describing the course and significance of separation anxiety in parents of firstborn infants. Although no gender effects were found in mean levels of separation anxiety across the 1st 2 years of parenthood, regression analyses revealed different patterns of relations between separation anxiety and psychological and contextual variables for men and women. For men, only self-criticism and their wife's separation anxiety were significant; for women, separation anxiety was related to personality attributes (such as dependency and self-criticism), role-related beliefs, their spouse's anxiety about separation, and the unique health characteristics of their child. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
100.
Bruder Gerard E.; Quitkin Frederic M.; Stewart Jonathan W.; Martin Candace; Voglmaier Martina M.; Harrison Wilma M. 《Canadian Metallurgical Quarterly》1989,98(2):177
Examined the influence of diagnostic subtype of depression on perceptual asymmetry for dichotic listening and visual tachistoscopic tasks. A total of 65 unmedicated patients with major depressive disorders and 30 normal controls were tested on a verbal and nonverbal task in each modality. Patients diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) with melancholia had abnormal perceptual asymmetry for dichotic nonsense syllable and complex tone tasks. In contrast, patients having a nonmelancholic "atypical depression" (reactivity of mood with preserved pleasure capacity and associated features) did not differ from normal controls on these tasks, but had an increased incidence of left handedness. Bipolar depression (history of hypomania) differed from unipolar depression in showing abnormal perceptual asymmetry for a tachistoscopic dot enumeration task. Alterations of perceptual asymmetry in melancholia and bipolar depression were consistent with hypothesized right hemisphere dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献