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排序方式: 共有721条查询结果,搜索用时 684 毫秒
141.
Electromagnetic fields (EMFs) disrupt the electrochemical balance of biological membranes, thereby causing abnormal cation movement and deterioration of the function of membrane voltage-gated ion channels. These can trigger an increase of oxidative stress (OS) and the impairment of all cellular functions, including DNA damage and subsequent carcinogenesis. In this review we focus on the main mechanisms of OS generation by EMF-sensitized NADPH oxidase (NOX), the involved OS biochemistry, and the associated key biological effects. 相似文献
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143.
Lukas Babylon Fabian Schmitt Yannik Franke Tim Hubert Gunter P. Eckert 《International journal of molecular sciences》2022,23(15)
Increased amyloid beta (Aβ) levels and mitochondrial dysfunction (MD) in the human brain characterize Alzheimer disease (AD). Folic acid, magnesium and vitamin B6 are essential micro-nutrients that may provide neuroprotection. Bioenergetic parameters and amyloid precursor protein (APP) processing products were investigated in vitro in human neuroblastoma SH-SY5Y-APP695 cells, expressing neuronal APP, and in vivo, in the invertebrate Caenorhabditis elegans (CL2006 & GMC101) expressing muscular APP. Model organisms were incubated with either folic acid and magnesium-orotate (ID63) or folic acid, magnesium-orotate and vitamin B6 (ID64) in different concentrations. ID63 and ID64 reduced Aβ, soluble alpha APP (sAPPα), and lactate levels in SH-SY5Y-APP695 cells. The latter might be explained by enhanced expression of lactate dehydrogenase (LDHA). Micronutrient combinations had no effects on mitochondrial parameters in SH-SY5Y-APP695 cells. ID64 showed a significant life-prolonging effect in C. elegans CL2006. Incubation of GMC101 with ID63 significantly lowered Aβ aggregation. Both combinations significantly reduced paralysis and thus improved the phenotype in GMC101. Thus, the combinations of the tested biofactors are effective in pre-clinical models of AD by interfering with Aβ related pathways and glycolysis. 相似文献
144.
Roxane Padrutt Dr. Vipin Babu Simon Klingler Martina Kalt Dr. Frank Schumer Maria I. Anania Lukas Schneider Prof. Bernhard Spingler 《ChemMedChem》2021,16(4):694-701
We report the synthesis of the first transplatin-BODIPY conjugates for application in photodynamic therapy (PDT). The distyryl BODIPYs containing two iodine atoms were designed to absorb in the red region, easily undergo intersystem crossing for efficient singlet oxygen generation, and additionally offer the possibility for coordination with mono-activated transplatin. We were able to demonstrate that coordination of the BODIPYs with a mono-activated transplatin increases the phototoxic index of the photosensitizers significantly, giving rise to highly phototoxic distyryl BODIPY derivatives, of which one was shown to have the highest ever reported phototoxic index against any cell line. Furthermore, the photophysical mechanism of singlet oxygen generation in distyryl BODIPYs undergoing intramolecular charge transfer was studied experimentally and using time-dependent density functional theory. 相似文献
145.
Urs Lindenmann Dr. Michael Brand Flavio Gall David Frasson Lukas Hunziker Dr. Ivana Kroslakova Prof. Dr. Martin Sievers Prof. Dr. Rainer Riedl 《ChemMedChem》2020,15(8):675-679
Sentrin-specific proteases (SENPs) are responsible for the maturation of small ubiquitin-like modifiers (SUMOs) and the deconjugation of SUMOs from their substrate proteins. Studies on prostate cancer revealed an overexpression of SENP1, which promotes prostate cancer progression as well as metastasis. Therefore, SENP1 has been identified as a novel drug target against prostate cancer. Herein, we report the discovery and biological evaluation of potent and selective SENP1 inhibitors. A structure-activity relationship (SAR) of the newly identified pyridone scaffold revealed allosteric inhibitors with very attractive in vitro ADMET properties regarding plasma binding and plasma stability for this challenging target. This study also emphasizes the importance of biochemical mode of inhibition studies for de novo designed inhibitors. 相似文献
146.
Dr. Lukas Greifenstein Dr. Nils Engelbogen Hanane Lahnif Dr. Jean-Philippe Sinnes Prof. Dr. Ralf Bergmann Prof. Dr. Michael Bachmann Prof. Dr. Frank Rösch 《ChemMedChem》2020,15(8):695-704
The L-lysine urea-L-glutamate (KuE) represents a key motif in recent diagnostic and therapeutic radiopharmaceuticals targeting the prostate specific membrane antigen (PSMA). Using a squaric acid moiety for coupling of KuE with a radioactive label, the squaric acid as a linker in the PSMA ligand seems to mimic the aromatic structure of the naphthylalanine unit on PSMA-617. In this work, we investigate the influence of squaric acid moiety on the biological activity of the compound carrying a KuE motif and three typical chelates. The derivatives TRAM.SA.KuE, DOTAGA.SA.KuE and NODAGA.SA.KuE were all synthesized in straightforward organic reactions and purified by HPLC afterward. Different amounts of tracer were labeled at different temperatures with 68Ga. PET examinations were performed on NMRInu/nu nude mice with an LNCaP tumor on the right hind leg including ex vivo investigations of the organs. For comparison, 68Ga-derivatives of PSMA-11 and PSMA-617, the derivatives most commonly used in clinics, were investigated in the same animal model. 相似文献
147.
Fluid dynamics in structured packings is investigated by X‐ray tomography. The focus is set on the influence of liquid viscosity varied between 5 and 50 mPa s. Film flow is the dominant flow pattern, but there are also contact‐point liquid patterns representing liquid accumulated at contact points between adjacent packing sheets. The holdup fractions of both flow patterns are quantified, and the average surface‐to‐volume ratio is determined. Furthermore, the wetting ratio of the structured packing is examined for different viscosities and liquid loads. 相似文献
148.
J Lukas J Bartkova M Welcker OW Petersen G Peters M Strauss J Bartek 《Canadian Metallurgical Quarterly》1995,10(11):2125-2134
To explore regulation and function of cyclin D2, a candidate cell cycle-regulatory proto-oncogene, we examined subcellular localisation, cell type- and cell cycle-dependent expression, and requirement of cyclin D2 protein for G1 progression, in a panel of 40 human normal and cancer cell types. Except for lymphoid cells and sarcoma cell lines, expression of cyclin D2 was considerably more restricted than that of cyclin D1, whereas both D-type cyclin proteins were low or undetectable in cells lacking functional retinoblastoma gene product. In G1 cells, the cyclin D2 protein was more resistant to extraction and localised predominantly to nuclei, whereas it became more soluble and distributed in both nuclei and cytoplasm from G1/S transition onwards. Centrifugal elutriation and multiparameter flow cytometry analyses of several cell types showed moderate cell cycle oscillation with maximum levels of the cyclin D2 protein reached in late G1. Microinjection and/or electroporation of antibodies to cyclin D2 during G1 arrested the cyclin D2-expressing lymphocytes, breast myoepithelium, and U-2-OS sarcoma cells in G1 phase, whereas cyclin D2-negative cell types were unaffected by such treatment. Consistent with the putative proto-oncogenic role of cyclin D2 in specific cell types, our data show that this G1 cyclin has properties closely resembling those of cyclin D1, including the essential positive role in regulation of G1. 相似文献
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