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排序方式: 共有1321条查询结果,搜索用时 31 毫秒
1.
Katja F. Hellendahl Felix Kaspar Dr. Xinrui Zhou Zhaoyi Yang Prof. Dr. Zhen Huang Prof. Dr. Peter Neubauer Dr. Anke Kurreck 《Chembiochem : a European journal of chemical biology》2021,22(11):2002-2009
Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes. 相似文献
2.
Jonas Ort Benedikt Kremer Linda Grüßer Romy Blaumeiser-Debarry Hans Clusmann Mark Coburn Anke Hllig Ute Lindauer 《International journal of molecular sciences》2020,21(23)
Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage. 相似文献
3.
Ching-Te Chuang Bernstein K. Joshi R.V. Puri R. Kim K. Nowak E.J. Ludwig T. Aller I. 《Circuits and Devices Magazine, IEEE》2004,20(1):6-19
The generation-over-generation scaling of critical CMOS technology parameters is ultimately bound by nonscalable limitations, such as the thermal voltage and the elementary electronic charge. Sustained improvement in performance and density has required the introduction of new device structures and materials. Partially depleted SOI, a most recent MOSFET innovation, has extended VLSI performance while introducing unique idiosyncrasies. Fully depleted SOI is one logical extension of this device design direction. Gate dielectric tunneling, device self-heating, and single-event upsets present developers of these next-generation devices with new challenges. Strained silicon and high-permittivity gate dielectric are examples of new materials that will enable CMOS developers to continue to deliver device performance enhancements in the sub-100 nm regime. 相似文献
4.
5.
W. S. Walston I. M. Bernstein A. W. Thompson 《Metallurgical and Materials Transactions A》1991,22(6):1443-1451
The microstructure of a single-crystal nickel-base superalloy, PWA 1480, has been varied by heat treatment and hot isostatic
pressing in order to study the role of the γ/yγ′ eutectic and porosity on subsequent tensile behavior. The level of porosity
was found not to affect any of the tensile properties, while the γ/γ′ eutectic strongly influenced ductility. Eliminating
the γ/γ′ eutectic increased ductility which was attributed to the cleavage fracture of this constituent. It is proposed that
such cleavage of the γ/γ′ eutectic is initiated by the stress created from impinging slip bands, promoting shear localization,
and final fracture along {111} slip planes. The precise nature of this fracture process is discussed with emphasis on the
role of the γ/′ micro-structure. The deformation structure of PWA 1480 was also studied, and while different in some respects
from many other single-crystal superalloys, its fracture process appears to be similar.
Formerly Graduate Student, Department of Metallurgical Engineering and Materials Science, Carnegie Mellon University. 相似文献
6.
7.
MS Ali PP Sayeski LB Dirksen DJ Hayzer MB Marrero KE Bernstein 《Canadian Metallurgical Quarterly》1997,272(37):23382-23388
Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors. 相似文献
8.
Temporal order and functional analysis of mutations within the Fli-1 and p53 genes during the erythroleukemias induced by F-MuLV 总被引:1,自引:0,他引:1
JC Howard S Yousefi G Cheong A Bernstein Y Ben-David 《Canadian Metallurgical Quarterly》1993,8(10):2721-2729
The erythroleukemias induced by Friend murine leukemia virus (F-MuLV) result from the accumulation of a number of genetic changes, including activation of the Fli-1 proto-oncogene and inactivation of the p53 tumor suppressor gene. We have determined the temporal order of mutation of the genes involved in this multistage malignancy, by serial in vivo transplantation of F-MuLV induced primary erythroleukemias into syngenic Balb/c mice. These primary tumors are capable of growing when transplanted into syngenic mice, but die after several days of in vitro culture. From the transplanted tumors grown in syngenic mice, erythropoietin-dependent cell lines were established in culture that are clonally related to cells in the primary tumors. We show that retroviral insertional activation of the Fli-1 ets family member is the first detectable genetic event in F-MuLV induced primary erythroleukemias. Mutations in the p53 gene were observed in the Epo-dependent cell lines but not in the transplanted erythroleukemias used to establish these cell lines in culture. These data suggest that activation of Fli-1 plays an important role in the early stages of F-MuLV-induced leukemia, perhaps by altering the self-renewal probabilities of erythroid progenitor cells and that p53 mutations immortalize these cells, enabling them to grow in vitro in the presence of Epo. 相似文献
9.
EF Bernstein FJ Sullivan JB Mitchell GD Salomon E Glatstein 《Canadian Metallurgical Quarterly》1993,20(3):435-453
Radiation therapy exerts both acute and chronic effects on normal tissue included within treatment fields. The physics of radiation therapy and treatment techniques to minimize deleterious effects of radiation are presented. Management of radiation-damaged skin is discussed. Radiation effect on tissue, wound healing, and tumorigenesis also are reviewed. 相似文献
10.
The human mineralocorticoid receptor of the steroid receptor family contains a modular structure with domain E which is considered to be a hormone binding domain. Recombinant protein approaches enabled us to clearly determine that this domain is also able to interact with F-actin (Kd about 2 microM) and G-actin. Moreover, it was revealed that this mineralocorticoid receptor domain/actin interaction was modulated by specific mineralocorticoid ligands. Agonist (aldosterone) steroid binding almost totally (91%) abolished the interaction with F-actin, while antagonist (progesterone) binding allowed more than 30% of this binding. Steroid modulation of the interaction between domain E and actin indicated that this actin binding is specific and could be essential for cellular mineralocorticoid receptor activity. 相似文献