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61.
The effectiveness of electrospinning as a simple approach to disperse POSS into a polymer matrix at a nm‐level has been assessed. Electrospun and cast films were prepared by dissolving CA and epoxycyclohexylisobutyl POSS in the solvent mixture acetone/DMAc. The membranes were characterized by SEM, TEM and WAXD. Whereas films produced by casting showed µm‐sized POSS crystals, thus suggesting a small affinity between the polymer matrix and the POSS molecules, those prepared by electrospinning were characterized by a nanometric POSS distribution. This is explained by considering the peculiar solvent evaporation mechanism, occurring during the electrospinning process, which allows to produce nanofibers characterized by a silsesquioxane dispersion similar to that present in solution.
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Dr. Erika Lisztes Dr. Erika Mező Fruzsina Demeter Lilla Horváth Dr. Szilvia Bősze Dr. Balázs István Tóth Prof. Anikó Borbás Dr. Mihály Herczeg 《ChemMedChem》2021,16(9):1467-1476
The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Herein, we present the efficient synthesis of five Glc-GlcA-Glc-sequenced and one Glc-IdoA-Glc-sequenced non-glycosaminoglycan, heparin-related trisaccharides with various sulfation/sulfonylation and methylation patterns. The cell growth inhibitory effects of the compounds were tested against four cancerous human cell lines and two non-cancerous cell lines. Two d -glucuronate-containing tetra-O-sulfated, partially methylated trisaccharides displayed remarkable and selective inhibitory effects on the growth of ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental, whereas acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives. 相似文献
63.
Peter K. Windsor Stephen P. Plassmeyer Dominic S. Mattock Jonathan C. Bradfield Erika Y. Choi Bill R. Miller III Byung Hee Han 《International journal of molecular sciences》2021,22(6)
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease. 相似文献
64.
Nitza Soto Karoll Ferrer Katy Díaz Csar Gonzlez Lautaro Taborga Andrs F. Olea Hctor Carrasco Luis Espinoza 《International journal of molecular sciences》2021,22(9)
Brassinosteroids are polyhydroxysteroids that are involved in different plants’ biological functions, such as growth, development and resistance to biotic and external stresses. Because of its low abundance in plants, much effort has been dedicated to the synthesis and characterization of brassinosteroids analogs. Herein, we report the synthesis of brassinosteroid 24-nor-5β-cholane type analogs with 23-benzoate function and 22,23-benzoate groups. The synthesis was accomplished with high reaction yields in a four-step synthesis route and using hyodeoxycholic acid as starting material. All synthesized analogs were tested using the rice lamina inclination test to assess their growth-promoting activity and compare it with those obtained for brassinolide, which was used as a positive control. The results indicate that the diasteroisomeric mixture of monobenzoylated derivatives exhibit the highest activity at the lowest tested concentrations (1 × 10−8 and 1 × 10−7 M), being even more active than brassinolide. Therefore, a simple synthetic procedure with high reaction yields that use a very accessible starting material provides brassinosteroid synthetic analogs with promising effects on plant growth. This exploratory study suggests that brassinosteroid analogs with similar chemical structures could be a good alternative to natural brassinosteroids. 相似文献
65.
HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors. 相似文献
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The Beaver Creek confluence with the main‐stem Klamath River was studied to assess salmonid use in a thermal mixing zone under various summer hydrological and meteorological conditions. Main‐stem flow releases from Iron Gate Dam ranged from 17 cms (615 cfs) to 37 cms (1320 cfs) during the study period and main‐stem water temperatures ranged from 19.5 to 26°C. A grid was constructed to define the thermal refuge as a system of cells. Temperatures were monitored using remote temperature loggers and fish counts were conducted using daytime snorkelling. Most juvenile salmonids were observed moving into the refuge when main‐stem temperatures exceeded 22–23°C. Salmonids in the thermal refuge did not necessarily seek the coolest water, but were generally located in habitats commensurate with species‐specific behavioural needs within their thermal tolerance range. Such ranges largely occurred within refuge areas. Variable meteorological conditions confounded observable biological thermal benefit to fish resulting from higher or lower main‐stem flows. Thermal regime dynamics indicated that under the hydrological and meteorological conditions observed, higher flows from Iron Gate Dam showed some ability to change the structure of the refuge area. It appeared that without the thermal refuge, main‐stem flows alone could not sustain the salmonid population because high water temperatures usually exceeded their published thermal tolerance limits. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
70.
During the summer in the main‐stem Klamath River, juvenile salmonids respond positively to cooler tributary temperatures by congregating in large schools at the mouths of these tributaries, referred to as thermal refugia. The purpose of this paper is to summarize results from coho salmon (Oncorhynchus kisutch) thermal refugia studies conducted since 2006 in the Klamath River. Results showed that juvenile coho salmon started using thermal refugia when the Klamath River main‐stem temperature approached approximately 19 °C. The majority of the juvenile coho salmon within the studied thermal refugia were found in the slower velocity habitat associated with cover. Juvenile coho salmon counts in the studied thermal refugia dramatically decreased at temperatures >22–23 °C, suggesting that this approximates their upper thermal tolerance level. Although some juvenile coho salmon were very mobile, others chose, until smoltification, to rear in the mouths and lower reaches of non‐natal tributaries where thermal refugia occurred, apparently because of suitable habitat conditions. Information gained from these investigations will improve our knowledge of the life history of coho salmon in the Klamath River drainage and how they use the main‐stem river. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献