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51.
Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents 下载免费PDF全文
Dr. Roberta Ettari Dr. Andrea Pinto Dr. Lucia Tamborini Dr. Ilenia C. Angelo Prof. Silvana Grasso Prof. Maria Zappalà Dr. Natale Capodicasa Dr. Laura Yzeiraj Dr. Esther Gruber Dr. Makoah N. Aminake Dr. Gabriele Pradel Prof. Tanja Schirmeister Prof. Carlo De Micheli Prof. Paola Conti 《ChemMedChem》2014,9(8):1817-1825
Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds. 相似文献
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Information on natural concentrations or variability of secondary metabolites in marine organisms may be important both to ecological/evolutionary and applied approaches. A gas chromatographic procedure with an electron capture detector (GC-ECD) was developed to quantify the sesquiterpenoid elatol at the surface and within-thalli of 70 specimens of the red seaweed Laurencia obtusa. The concentration of elatol was highest within-thalli [9.89 mg g−1 of L. obtusa, dry weight (d.w.)], compared to lower values found at the surface [0.006 mg g−1 of L.obtusa (d.w.), or 0.5–10.0 ng cm−2]. This method provides a rapid and inexpensive quantification of small quantities of elatol, and probably may also be used to quantify other halogenated compounds usually found in red seaweeds. 相似文献
54.
Michele Espinosa da Cunha Laiza Canielas Krause Maria Silvana Aranda Moraes Candice Schmitt Faccini Rosângela Assis Jacques Suelen Rodrigues Almeida Maria Regina Alves Rodrigues Elina Bastos Caramão 《Fuel Processing Technology》2009
In the present work, the process of biodiesel production in a pilot plant has been studied using beef tallow as raw materials with methanol and potassium hydroxide as catalyst. The biodiesel quality is regulated by Brazilian specifications (Resolution 42) by the National Agency of Petroleum (ANP). The alkaline transesterification of animal fat with methanol produces a biodiesel with high quality and also with a good conversion rate. The process is possible but the economical viability must be improved by recovering methanol and glycerin. The obtained results have been used for industrial scale up of the process. 相似文献
55.
Walter Luiz Andrade de Oliveira Silvana De Nardin Ana Lúcia H. de Cresce El Debs Mounir Khalil El Debs 《Journal of Constructional Steel Research》2009,65(12):2103-2110
This paper presents an experimental analysis of the confinement effects in steel–concrete composite columns regarding two parameters: concrete compressive strength and column slenderness. Sixteen concrete-filled steel tubular columns with circular cross section were tested under axial loading. The tested columns were filled by concrete with compressive strengths of 30, 60, 80, and 100 MPa, and had length/diameter ratios of 3, 5, 7, and 10. The experimental values of the columns’ ultimate load were compared to the predictions of 4 code provisions: the Brazilian Code NBR 8800:2008, Eurocode 4 (EN 1994-1-1:2004), AINSI/AISC 360:2005, and CAN/CSA S16-01:2001. According to the results, the load capacity of the composite columns increased with increasing concrete strength and decreased with increasing length/diameter ratio. In general, the code provisions were highly accurate in the prediction of column capacity. Among them, the Brazilian Code was the most conservative, while Eurocode 4 presented the values closest to the experimental results. 相似文献
56.
Stefano De Benedetti Elisabetta Gianazza Cristina Banfi Alessandro Marocchi Christian Lunetta Silvana Penco Francesco Bonomi Stefania Iametti 《Proteomics. Clinical applications》2017,11(11-12)
This study is meant to characterize the serum proteome in a small geographical cluster of sporadic ALS subjects originating from a restricted geographical area and sharing the same environmental exposure, in a broader context of evaluating the relevance of environmental factors to disease onset, status, and progression. An Artificial Neural Network based software is used to compare the relative abundance of proteins identified as different (by means of bi‐dimensional electrophoresis and mass spectrometry) in the serum proteome of patients and age‐matched healthy controls. The patient's group is characterized by altered levels of acute phase reactants and of proteins involved in lipid homeostasis, along with over‐representation of the APOE*4 allele. Characterization of the serum proteome in a small cluster of sporadic ALS patients, originating from a geographically restricted area with a high prevalence of the disease and evaluation of the results with software based on artificial neural networks, highlights the association of the relative abundance of some proteins (most notably, acute phase reactants and lipid homeostasis proteins) with the disease presence and status. 相似文献
57.
Mackeler Ramos Polassi Rebeca de Macedo Ferreira Almeida Silvana Coelho de Arruda Barbosa Nádia da Rocha Svizero 《Journal of Adhesion Science and Technology》2018,32(10):1033-1043
Purpose: The present study evaluated the influence of the hyaluronic acid (HA) on the bonding ability of self-adhesive resin cements to dentin regarding the bond strength. Eighty bovine incisors were ground flat to obtain a 2-mm thick slices which received conical preparations. The specimens were randomly distributed into 4 groups (n = 15) according to the dentin pretreatment (1 – control: untreated dentin; 2 – application of HA) and the evaluation time (1 – control: immediate evaluation; 2 – hydrolytic degradation: 6 months of storage in water at 37 °C). Preparations received the application of a self-adhesive resin cement (RelyX U200 or MaxCem Elite). Push-out bond strength test was conducted (0.5 mm/min). The bond strength data was submitted to two-way ANOVA/Tukey’s test (α = 0.05). For U200, no significance was observed when comparing the immediate (24 h) and 6 months means for the control groups (unexposed specimens). Previous application of HA to dentin significantly reduced the bond strength of U200 to dentin in both evaluation times (p < 0.05). HA had no significant influence on the push-out bond strength means for the cement MAX in both evaluation times (p > 0.05). The type 1 failure mode (adhesive mode) occurred in 100% of the specimens, irrespective of the dentin treatment or evaluation times. Pretreatment of dentin with HA produces a material-dependent influence on the push-out bond strength. The bonding ability of RelyX U200 is negatively influenced by the pretreatment of dentin with HA, whereas the biomodification of dentin with this bioactive agent causes no impact for the cement MaxCem Elite. 相似文献
58.
Viganò L Arillo A Buffagni A Camusso M Ciannarella R Crosa G Falugi C Galassi S Guzzella L Lopez A Mingazzini M Pagnotta R Patrolecco L Tartari G Valsecchi S 《Water research》2003,37(3):501-518
Comprehensive and contemporary evaluations of physical, chemical and toxicological endpoints have been performed on bed sediments of the Po River, the major Italian watercourse. Two extensive sampling campaigns were conducted in summer and winter low-flow conditions. Composite sediment samples were collected from ten reaches of the main river: the first was located in the upper region (ambient control), and the others downstream of the confluences of nine principal tributaries. The two sampling programs were paralleled by contemporary investigations on the macroinvertebrate community. The particle-size composition along the Po River showed a relatively uniform distribution of fine sand, a progressive downstream decrease of coarse sands and a corresponding increase of fine materials. The levels of polychlorinated biphenyls (PCB), polycyclic aromatic hydrocarbons (PAH), extractable organo halides (EOX), Cd, Cr, Cu, Hg, Ni, Pb and Zn were determined in sediment fine particles (< 63 microm), and showed marked changes across the ten river reaches. Their longitudinal trends, as those of organic carbon and total nitrogen, were very similar and largely independent of the survey season. Sediment quality benchmarks were used to evaluate sediment chemistry, and, although the overall level of contamination was from moderate to low, the reaches located downstream of the tributaries Dora Riparia, Dora Baltea, Lambro and Oglio were considered to be at risk. Sediments were tested for toxicity on Oncorhynchus mykiss, Ceriodaphnia dubia, Raphidocelis subcapitata and Vibrio fischeri. The toxicity tests were conducted both with sediment extracts and whole samples. Sediment extracts showed toxic potentials that were consistent with the spatial distribution of contaminants. Whole-sediment toxicity showed moderate/low effects which also included false positives and negatives. Alterations of the macroinvertebrate community were found for many kilometers downstream of Dora Riparia, and with a seasonal dependence, also in other reaches of the Italian river. Principal component analysis (PCA) was used to describe the longitudinal and temporal changes of the Po River, and allowed the selection of the most useful and discriminating indicators. 相似文献
59.
Nunzia Novizio Raffaella Belvedere Emanuela Pessolano Silvana Morello Alessandra Tosco Pietro Campiglia Amelia Filippelli Antonello Petrella 《International journal of molecular sciences》2021,22(20)
The tumor microenvironment (TME) is a dynamic system where nontumor and cancer cells intercommunicate through soluble factors and extracellular vesicles (EVs). The TME in pancreatic cancer (PC) is critical for its aggressiveness and the annexin A1 (ANXA1) has been identified as one of the oncogenic elements. Previously, we demonstrated that the autocrine/paracrine activities of extracellular ANXA1 depend on its presence in EVs. Here, we show that the complex ANXA1/EVs modulates the macrophage polarization further contributing to cancer progression. The EVs isolated from wild type (WT) and ANXA1 knock-out MIA PaCa-2 cells have been administrated to THP-1 macrophages finding that ANXA1 is crucial for the acquisition of a protumor M2 phenotype. The M2 macrophages activate endothelial cells and fibroblasts to induce angiogenesis and matrix degradation, respectively. We have also found a significantly increased presence of M2 macrophage in mice tumor and liver metastasis sections previously obtained by orthotopic xenografts with WT cells. Taken together, our data interestingly suggest the relevance of ANXA1 as potential diagnostic/prognostic and/or therapeutic PC marker. 相似文献
60.
It is becoming evident that sustainable development methods are now being considered by governments and corporations from all countries at both local and global level. Firms are increasingly looking to strike a balance between profit, preserving the local environment, and energy savings, rather than just looking for profit. In this paper, an enterprise input–output analysis based on production processes is used to investigate two tile manufacturers, one located in China and the other in Italy. The aim of the paper is to describe their energy/materials use and consequent pollution/waste emissions, and to make a comparison between them. As this industry uses huge quantities of energy, it is useful to monitor these consumption uses along with pollution levels. This accounting can help in planning future local development strategies that would make production cycles more efficient and sustainable. 相似文献