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81.
Saliha Harrach Jasmin Haag Martin Steinbüchel Rita Schrter Ute Neugebauer Jessica Bertrand Giuliano Ciarimboli 《International journal of molecular sciences》2022,23(22)
Tyrosine kinase inhibitors (TKI) such as Masitinib were reported to be useful as therapeutic options in malignant disorders and nonmalignant diseases, like coronavirus disease 2019 (COVID-19). Most kinases must be translocated into targeted cells by the action of specific transport proteins, as they are hydrophilic and not able to cross cell membranes freely. Accordingly, the efficacy of TKI in target cells is closely dependent on the expression of their transporters. Specifically, Masitinib is an organic cation and is expected to interact with organic cation transporters (OCT and Multidrug and Toxin Extrusion proteins—MATE-). The aim of this work was to characterize the interaction of Masitinib with different OCTs. Human embryonic kidney 293 cells stably transfected with murine or human OCT were used for the experiments. The interaction of Masitinib with OCTs was investigated using quenching experiments. The intracellular accumulation of this drug was quantified using high performance liquid chromatography. Our results identified interactions of Masitinib with almost all investigated mouse (m) and human (h) OCTs and hMATE1 and indicated OCT1 and hOCT2 to be especially potent Masitinib translocators across cell membranes. Interestingly, some important differences were observed for the interaction with murine and human OCTs. In the future, investigations concerning further in vitro and in vivo properties of Masitinib and its efficacy related to transporter-related uptake mechanisms under pathophysiological conditions should be performed. Clinical trials in humans and other animals with Masitinib have already shown promising results. However, further research is necessary to understand the disease specific transport mechanisms of Masitinib to contribute to a successful and responsible therapy employment. 相似文献
82.
Giacomina Rossi Erika Salvi Luisa Benussi Elkadia Mehmeti Andrea Geviti Sonia Bellini Antonio Longobardi Alessandro Facconi Matteo Carrara Cristian Bonvicini Roland Nicsanu Claudia Saraceno Martina Ricci Giorgio Giaccone Giuliano Binetti Roberta Ghidoni 《International journal of molecular sciences》2022,23(21)
Genetic frontotemporal lobar degeneration (FTLD) is characterized by heterogeneous phenotypic expression, with a disease onset highly variable even in patients carrying the same mutation. Herein we investigated if variants in lysosomal genes modulate the age of onset both in FTLD due to GRN null mutations and C9orf72 expansion. In a total of 127 subjects (n = 74 GRN mutations and n = 53 C9orf72 expansion carriers), we performed targeted sequencing of the top 98 genes belonging to the lysosomal pathway, selected based on their high expression in multiple brain regions. We described an earlier disease onset in GRN/C9orf72 pedigrees in subjects carrying the p.Asn521Thr variant (rs1043424) in PTEN-induced kinase 1 (PINK1), a gene that is already known to be involved in neurodegenerative diseases. We found that: (i) the PINK1 rs1043424 C allele is significantly associated with the age of onset; (ii) every risk C allele increases hazard by 2.11%; (iii) the estimated median age of onset in homozygous risk allele carriers is 10–12 years earlier than heterozygous/wild type homozygous subjects. A replication study in GRN/C9orf72 negative FTLD patients confirmed that the rs1043424 C allele was associated with earlier disease onset (−5.5 years in CC versus A carriers). Understanding the potential mechanisms behind the observed modulating effect of the PINK1 gene in FTLD might prove critical for identifying biomarkers and/or designing drugs to modify the age of onset, especially in GRN/C9orf72-driven disease. 相似文献
83.
84.
A Giuliano M Papenfuss J Guernsey De Zapien S Tilousi L Nuvayestewa 《Canadian Metallurgical Quarterly》1998,8(3):160-167
To describe the geographical patterns and trends of macronutrient intake in Japan for the recent 20 years, we analyzed the data sets of the National Nutrition Surveys (J-NNS). First, we calculated regression coefficients for survey year by prefecture for energy, protein, fat, and carbohydrate intake. These results, however, could be affected by the changes in age and sex distributions of the survey samples. Secondly, as the food consumption data were based on household as a unit, we used proportions of the subjects who belong to age-specific groups and female subjects in a sub-sample for each prefecture in a given year for adjustment by general lineal model. As a result, 1% increase in the subjects aged 1-4, 10-19 and 65- years and female subjects was equivalent to the changes in average energy intake by -5.88, +2.27, -1.45 and -1.62 kcal, respectively. After the adjustment for age and sex, number of significant negative coefficients among 47 prefectures decreased for energy and carbohydrate intake, and that of positive coefficients increased for fat intake. This suggested that unadjusted trend data might lead to an overestimation of decreasing trends of energy and carbohydrate intake, and an underestimation of increasing trend of fat intake in the recent 20 years. 相似文献
85.
The Campagna Romana, a landscape of unrivalled historical and cultural importance, can be subdivided into three main sectors, characterised by different plant communities, climate, geology and impact of man; these are the west sector, the river Tiber and the east sector. This landscape typology is a striking example of man-environment interaction: its primary source is in different climatic and geological conditions of these three sectors , but it was strongly reinforced by different land use. The western sector has been conserved in a semi-natural state until recent times while the eastern sector, characterised by communities influenced by man and ruins, has been almost completely devoid of woody vegetation probably since the Roman Empire. 相似文献
86.
The energy market is undergoing major changes, the most notable of which is the transition from a hierarchical closed system toward a more open one highly based on a ??smart?? information-rich infrastructure. This transition calls for new information and communication technologies infrastructures and standards to support it. In this paper, we review the current state of affairs and the actual technologies with respect to such transition. Additionally, we highlight the contact points between the needs of the future grid and the advantages brought by service-oriented architectures. 相似文献
87.
Masuhiro Tsukada Giuliano Freddi Masaaki Matsumura Hideki Shiozaki Nobutami Kasai 《应用聚合物科学杂志》1992,44(5):799-805
The structural characteristics, physical properties, and dyeing behavior of Bombyx mori silk fibers containing ethoxyethylmethacrylate (ETMA) polymer are reported in relation to the add-on. The add-on value increased with the reaction time and attained a maximum after 60 min at 80°C. The surface of silk fibers with an add-on value of 40% showed the presence of several irregular granules, consisting of ETMA oligomers. The infrared spectrum of the silk fibers containing the ETMA polymer showed overlapped absorption bands due to the molecular conformation of untreated silk and ETMA polymer, giving evidence that the ETMA polymerization occurred inside the fiber matrix. The DSC results suggested that the thermal decomposition behavior of the silk fiber remained almost unchanged, except that the decomposition temperature shifted slightly to higher temperature. The tensile properties of the silk fiber remained unchanged regardless of the ETMA polymerization. The rate and extent of acid dye uptake was greatly increased by the polymerization of ETMA into the silk fibers as well as the transfer printing properties. 相似文献
88.
Masuhiro Tsukada Yoko Goto Giuliano Freddi Takashi Yamamoto Nobuo Nakabayashi 《应用聚合物科学杂志》1992,44(12):2197-2202
The molecular weight distribution of poly-methyl methacrylate (poly-MMA) chains separated from MMA-grafted silk fibers obtained by using potassium persulfate (KPS) and tri-n-butylborane (TBB) as initiator of the graft-copolymerization reaction have been examined by gel permeation chromatography (GPC). GPC elution pattern of poly-MMA chains shows a bimodal molecular weight distribution. The two peaks have been identified as heavy and light component. The average molecular weight of the heavy component ranges from 48.5 to 200 kD for poly-MMA copolymerized by the KPS reaction system and from 336 to 816 kD for the poly-MMA copolymerized by the TBB reaction system. The light component has an average molecular weight lower than 1,000 D and its value is almost similar in all the samples examined. Scanning electron microscopy (SEM) analysis revealed the presence of MMA oligomers formed on the fiber surface during grafting. The molar ratio between poly-MMA chains and silk fibroin attains a constant value that seems to be specific for a certain reaction system. A linear correlation has been observed between the weight gain and the average molecular weight of the poly-MMA chains. These findings suggest the effect of grafting parameters on the molecular weight and molecular weight distribution of the grafted polymer, as well as its influence on the physical properties and textile performances of MMA-grafted silk fibers. 相似文献
89.
We present a simple model which permits to obtain the number of metallic clusters entrapped in Y zeolites from the curves of the chemical shifts of129Xe NMR against the pressure of Xe. From the metal loading the average number of atoms per cluster can also be calculated. We apply the model to Pt/NaY and the bimetallic Pt-Cu/NaY. 相似文献
90.
Giovanni Ambrosi Simona Bartocci Laurent Basara Roberto Battiston William J. Burger Luca Carfora Guido Castellini Piero Cipollone Livio Conti Andrea Contin Cinzia De Donato Cristian De Santis Francesco M. Follega Cristina Guandalini Maria Ionica Roberto Iuppa Giuliano Laurenti Ignazio Lazzizzera Mauro Lolli Christian Manea Laura Marcelli Giuseppe Masciantonio Matteo Mergé Giuseppe Osteria Lorenzo Pacini Francesco Palma Federico Palmonari Beatrice Panico Laura Patrizii Francesco Perfetto Piergiorgio Picozza Michele Pozzato Matteo Puel Irina Rashevskaya Ester Ricci Marco Ricci Sergio Bruno Ricciarini Valentina Scotti Alessando Sotgiu Roberta Sparvoli Bruno Spataro Vincenzo Vitale 《中国科学:技术科学(英文版)》2018,61(5):643-652
CSES(China Seismo-Electromagnetic Satellite) is a mission developed by CNSA(Chinese National Space Administration) and ASI(Italian Space Agency), to investigate the near-Earth electromagnetic, plasma and particle environment, for studying the seismo-associated disturbances in the ionosphere-magnetosphere transition zone. The anthropogenic and electromagnetic noise,as well as the natural non-seismic electromagnetic emissions is mainly due to tropospheric activity. In particular, the mission aims to confirming the existence of possible temporal correlations between the occurrence of earthquakes for medium and strong magnitude and the observation in space of electromagnetic perturbations, plasma variations and precipitation of bursts with highenergy charged particles from the inner Van Allen belt. In this framework, the high energy particle detector(HEPD) of the CSES mission has been developed by the Italian LIMADOU Collaboration. HEPD is an advanced detector based on a tower of scintillators and a silicon tracker that provides good energy and angular resolution and a wide angular acceptance, for electrons of 3–100 Me V, protons of 30–200 Me V and light nuclei up to the oxygen. CSES satellite has been launched on February 2~(nd), 2018 from the Jiuquan Satellite Launch Center(China). 相似文献