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161.
162.
Dr. Holger Siebeneicher Dr. Arwed Cleve Dr. Hartmut Rehwinkel Dr. Roland Neuhaus Dr. Iring Heisler Dr. Thomas Müller Dr. Marcus Bauser Dr. Bernd Buchmann 《ChemMedChem》2016,11(20):2261-2271
Despite the long‐known fact that the facilitative glucose transporter GLUT1 is one of the key players safeguarding the increase in glucose consumption of many tumor entities even under conditions of normal oxygen supply (known as the Warburg effect), only few endeavors have been undertaken to find a GLUT1‐selective small‐molecule inhibitor. Because other transporters of the GLUT1 family are involved in crucial processes, these transporters should not be addressed by such an inhibitor. A high‐throughput screen against a library of ~3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N‐(1H‐pyrazol‐4‐yl)quinoline‐4‐carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure–activity relationship explorations, single‐digit nanomolar inhibitors with a selectivity factor of >100 against GLUT2, GLUT3, and GLUT4 were obtained. The most promising compound, BAY‐876 [N4‐[1‐(4‐cyanobenzyl)‐5‐methyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐4‐yl]‐7‐fluoroquinoline‐2,4‐dicarboxamide], showed good metabolic stability in vitro and high oral bioavailability in vivo. 相似文献
163.
Martin Oschatz Marcus Rose Nicole Klein Thomas Freudenberg Gleb Yushin 《Carbon》2010,48(14):3987-3992
A hierarchical and highly porous carbide-derived carbon (CDC) was obtained by nanocasting of pre-ceramic precursors into cubic ordered silica (KIT-6) and subsequent chlorination. Resulting CDC replica materials show high methane and n-butane uptake and excellent performance as electrode materials in supercapacitors. 相似文献
164.
Cara Cocking Stephan Helling Marcus Oswald Peter Rammelsberg Gerhard Reinelt Alexander J. Hassel 《Color research and application》2010,35(3):233-239
A key criterion in the design of dental shade guides used for matching tooth color is that the shade tabs cover the natural tooth color space as completely as possible with a manageable number of tabs. Earlier studies have designed hypothetical shade guides from a given population of tooth colors described in the CIELAB system using the goal of minimizing the mean coverage error. In this study, we investigate this topic using the goal of maximizing coverage, meaning that as many measured colors as possible were within a given color difference from the nearest shade tab of the guide. We use techniques of linear discrete optimization to determine the positions of the shade tabs and consider both color difference formulas, CIELAB and CIEDE2000, in an exemplary tooth color population. We obtain coverage error and coverage figures for hypothetical shade guides of various numbers of tabs designed with the goal of either minimizing coverage error or maximizing coverage. Results show that discrete optimization and the goal of maximizing coverage could be used to improve shade guide development. The described technique could be used not only for dental shade guides development, but also for any purpose requiring coverage of as many colors as possible while keeping the number of reference colors manageable. © 2009 Wiley Periodicals, Inc. Col Res Appl, 2010 相似文献
165.
云南-广东±800 kV特高压直流输电工程基本设计 总被引:1,自引:0,他引:1
云南-广东±800 kV特高压直流输电项目目前正在建设中.这是中国很重要并极具技术含量的直流输电工程之一,它通过1 418 km长的直流输电线路将云南省的楚雄和广东省的穗东连接起来,设计输送容量为5 000 MW,是世界上最大的双极直流输电项目.文中介绍了云南-广东±800kV特高压直流输电项目的重点和难点,包括换流站整体设计原则以及增加的稳态和暂态电压应力对主设备设计提出的挑战,讨论了关键特高压直流设备的特殊设计概念. 相似文献
166.
Strength Degradation and Failure Mechanisms of Electron-Beam Physical-Vapor-Deposited Thermal Barrier Coatings 总被引:2,自引:0,他引:2
James A. Ruud i Bartz Marcus P. Borom Curtis A. Johnson 《Journal of the American Ceramic Society》2001,84(7):1545-1552
Failure mechanisms were determined for electron-beam physical-vapor-deposited thermal barrier coating (TBC) systems from the degradation of mechanical properties and microstructural changes in a furnace cycle test. Bond strength degradation for TBCs resulted from the initiation and growth of interfacial delamination defects between the yttria-stabilized zirconia topcoat and the thermally grown alumina (TGO). It is proposed that defects started from concave depressions in the bondcoat surface created by the grit-blast-cleaning process and that defect growth was driven by the reduction in compressive strain in the TGO as the alumina deformed into and displaced the bondcoat during the cooling cycles. Inclusion of yttrium in the substrate resulted in a doubling of the furnace cycle life of the TBCs because of enhanced fracture toughness of the TGO-bondcoat interface. 相似文献
167.
The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin 总被引:1,自引:0,他引:1
Glycosylated amino acids and glycosylated human serum albumin reduce nitrite to nitric oxide under anaerobic conditions. The amount of nitric oxide produced was recorded by generation of nitrosoHb from deoxyHb. Without preincubation after the addition of sodium nitrite, glucose or a mixture of glucose with amino acid or serum albumin did not cause spectrophotometrically detectible transformation of deoxyHb into nitrosoHb. The generation of NO increased with an increase in content of colored "final" products of amino acid and serum albumin glycosylation in the incubation mixture. The incubation of blood plasma of patients with diabetes mellitus with nitrite also resulted in the increased production of NO as compared to blood plasma of healthy subjects. During the incubation of healthy subjects' blood plasma with nitrite a small amount of NO was produced. The removal of low-molecular-weight compounds was accompanied by a significantly decreased generation of NO by blood plasma. 相似文献
168.
Annarita Falanga Valentina Del Genio Elizabeth A. Kaufman Carla Zannella Gianluigi Franci Marcus Weck Stefania Galdiero 《International journal of molecular sciences》2021,22(12)
Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol–ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics. 相似文献
169.
170.
Marcus Felipe Botacin Paulo Lício de Geus André Ricardo Abed Grégio 《Journal in Computer Virology》2018,14(1):87-98
In order to thwart dynamic analysis and bypass protection mechanisms, malware have been using several file formats and evasive techniques. While publicly available dynamic malware analysis systems are one of the main sources of information for researchers, security analysts and incident response professionals, they are unable to cope with all types of threats. Therefore, it is difficult to gather information from public systems about CPL, .NET/Mono, 64-bits, reboot-dependent, or malware targeting systems newer than Windows XP, which result in a lack of understanding about how current malware behave during infections on modern operating systems. In this paper, we discuss the challenges and issues faced during the development of this type of analysis system, mainly due to security features available in NT 6.x kernel versions of Windows OS. We also introduce a dynamic analysis system that addresses the aforementioned types of malware as well as present results obtained from their analyses. 相似文献