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991.
Magdalena Wujak Christine Veith Cheng-Yu Wu Tessa Wilke Zeki Ilker Kanbagli Tatyana Novoyatleva Andreas Guenther Werner Seeger Friedrich Grimminger Natascha Sommer Ralph Theo Schermuly Norbert Weissmann 《International journal of molecular sciences》2021,22(19)
Increased proliferation of pulmonary arterial smooth muscle cells (PASMCs) in response to chronic hypoxia contributes to pulmonary vascular remodeling in pulmonary hypertension (PH). PH shares numerous similarities with cancer, including a metabolic shift towards glycolysis. In lung cancer, adenylate kinase 4 (AK4) promotes metabolic reprogramming and metastasis. Against this background, we show that AK4 regulates cell proliferation and energy metabolism of primary human PASMCs. We demonstrate that chronic hypoxia upregulates AK4 in PASMCs in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. RNA interference of AK4 decreases the viability and proliferation of PASMCs under both normoxia and chronic hypoxia. AK4 silencing in PASMCs augments mitochondrial respiration and reduces glycolytic metabolism. The observed effects are associated with reduced levels of phosphorylated protein kinase B (Akt) as well as HIF-1α, indicating the existence of an AK4-HIF-1α feedforward loop in hypoxic PASMCs. Finally, we show that AK4 levels are elevated in pulmonary vessels from patients with idiopathic pulmonary arterial hypertension (IPAH), and AK4 silencing decreases glycolytic metabolism of IPAH-PASMCs. We conclude that AK4 is a new metabolic regulator in PASMCs interacting with HIF-1α and Akt signaling pathways to drive the pro-proliferative and glycolytic phenotype of PH. 相似文献
992.
Sylwia Sudo Agnieszka Cios Magdalena Jastrzbska-Wisek Ewelina Honkisz-Orzechowska Barbara Mordyl Natalia Wilczyska-Zawal Grzegorz Sataa Katarzyna Kucwaj-Brysz Anna Partyka Gniewomir Latacz Agnieszka Olejarz-Maciej Anna Wesoowska Jadwiga Handzlik 《International journal of molecular sciences》2021,22(19)
Among the serotonin receptors, one of the most recently discovered 5-HT6 subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. However, none of its selective ligands have reached the pharmaceutical market yet. Recently, a new chemical class of potent 5-HT6 receptor agents, the 1,3,5-triazine-piperazine derivatives, has been synthesized. Three members, the ortho and meta dichloro- (1,2) and the unsubstituted phenyl (3) derivatives, proved to be of special interest due to their high affinities (1,2) and selectivity (3) toward 5-HT6 receptor. Thus, a broader pharmacological profile for 1–3, including comprehensive screening of the receptor selectivity and drug-like parameters in vitro as well as both, pharmacokinetic and pharmacodynamic properties in vivo, have been investigated within this study. A comprehensive analysis of the obtained results indicated significant procognitive-like activity together with beneficial drug-likeness in vitro and pharmacokinetics in vivo profiles for both, (RS)-4-[1-(2,3-dichlorophenoxy)propyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (2) and (RS)-4-(4-methylpiperazin-1-yl)-6-(1-phenoxypropyl)-1,3,5-triazin-2-amine (3), but insensibly predominant for compound 2. Nevertheless, both compounds (2 and 3) seem to be good Central Nervous System drug candidates in search for novel therapeutic approach to dementia diseases, based on the 5-HT6 receptor target. 相似文献
993.
Daria Chlebek Tomasz Pociniczak Sara Gobetti Agata Kumor Katarzyna Hupert-Kocurek Magdalena Pacwa-Pociniczak 《International journal of molecular sciences》2022,23(1)
The Pseudomonas qingdaonensis ZCR6 strain, isolated from the rhizosphere of Zea mays growing in soil co-contaminated with hydrocarbons and heavy metals, was investigated for its plant growth promotion, hydrocarbon degradation, and heavy metal resistance. In vitro bioassays confirmed all of the abovementioned properties. ZCR6 was able to produce indole acetic acid (IAA), siderophores, and ammonia, solubilized Ca3(PO4)2, and showed surface active properties and activity of cellulase and very high activity of 1-aminocyclopropane-1-carboxylic acid deaminase (297 nmol α-ketobutyrate mg−1 h−1). The strain degraded petroleum hydrocarbons (76.52% of the initial hydrocarbon content was degraded) and was resistant to Cd, Zn, and Cu (minimal inhibitory concentrations reached 5, 15, and 10 mM metal, respectively). The genome of the ZCR6 strain consisted of 5,507,067 bp, and a total of 5055 genes were annotated, of which 4943 were protein-coding sequences. Annotation revealed the presence of genes associated with nitrogen fixation, phosphate solubilization, sulfur metabolism, siderophore biosynthesis and uptake, synthesis of IAA, ethylene modulation, heavy metal resistance, exopolysaccharide biosynthesis, and organic compound degradation. Complete characteristics of the ZCR6 strain showed its potential multiway properties for enhancing the phytoremediation of co-contaminated soils. To our knowledge, this is the first analysis of the biotechnological potential of the species P. qingdaonensis. 相似文献
994.
Magdalena Ka
mierczak Bartosz Trzaskowski Silvio Osella 《International journal of molecular sciences》2022,23(1)
An artificial leaf is a concept that not only replicates the processes taking place during natural photosynthesis but also provides a source of clean, renewable energy. One important part of such a device are molecules that stabilize the connection between the bioactive side and the electrode, as well as tune the electron transfer between them. In particular, nitrilotriacetic acid (NTA) derivatives used to form a self-assembly monolayer chemisorbed on a graphene monolayer can be seen as a prototypical interface that can be tuned to optimize the electron transfer. In the following work, interfaces with modifications of the metal nature, backbone saturation, and surface coverage density are presented by means of theoretical calculations. Effects of the type of the metal and the surface coverage density on the electronic properties are found to be key to tuning the electron transfer, while only a minor influence of backbone saturation is present. For all of the studied interfaces, the charge transfer flow goes from graphene to the SAM. We suggest that, in light of the strength of electron transfer, Co2+ should be considered as the preferred metal center for efficient charge transfer. 相似文献
995.
Sylwia K. Krl Ewa Bbenek Magdalena Dmoszyska-Graniczka Adrianna Sawiska-Brych Stanisaw Boryczka Andrzej Stepulak 《International journal of molecular sciences》2021,22(22)
Neuroblastoma (NB) and rhabdomyosarcoma (RMS), the most common pediatric extracranial solid tumors, still represent an important clinical challenge since no effective treatment is available for metastatic and recurrent disease. Hence, there is an urgent need for the development of new chemotherapeutics to improve the outcome of patients. Betulin (Bet), a triterpenoid from the bark of birches, demonstrated interesting anti-cancer potential. The modification of natural phytochemicals with evidenced anti-tumor activity, including Bet, is one of the methods of receiving new compounds for potential implementation in oncological treatment. Here, we showed that two acetylenic synthetic Bet derivatives (ASBDs), EB5 and EB25/1, reduced the viability and proliferation of SK-N-AS and TE671 cells, as measured by MTT and BrdU tests, respectively. Moreover, ASBDs were also more cytotoxic than temozolomide (TMZ) and cisplatin (cis-diaminedichloroplatinum [II], CDDP) in vitro, and the combination of EB5 with CDDP enhanced anti-cancer effects. We also showed the slowdown of cell cycle progression at S/G2 phases mediated by EB5 using FACS flow cytometry. The decreased viability and proliferation of pediatric cancers cells after treatment with ASBDs was linked to the reduced activity of kinases Akt, Erk1/2 and p38 and the induction of apoptosis, as investigated using Western blotting and FACS. In addition, in silico analyses of the ADMET profile found EB5 to be a promising anti-cancer drug candidate that would benefit from further investigation. 相似文献
996.
Lucyna Lewiska-Preis Ewa Szram Monika J.Fabiaska dám Nádudvari Magdalena Misz-Kennan Anna Abramowicz ukasz Kruszewski Andrzej Kita 《国际煤炭科学技术学报(英文)》2021,8(4):790-814
Many temporary and permanent reservoirs of water occur on or near coal-waste dumps in the Lower-and Upper Silesian Coal Basins (Poland).Little or nothing is kno... 相似文献
997.
Kamil Kornaus Radosław Lach Magdalena Szumera Konrad Świerczek Agnieszka Gubernat 《Journal of the European Ceramic Society》2019,39(7):2535-2544
The synthesis of tialite was carried out by means of the solid state reaction technique using heterogeneous nucleation. The influence of the temperature of synthesis and simultaneous sintering (1250–1350 °C) on the yield of reaction and densification of the systems was investigated. Reference samples, consisting of stoichiometric mixture of titanium and aluminium oxides as well as the samples containing such additives as MgO, SiO2 and MgTi2O5 were prepared. Applying the DSC analysis the synthesis temperatures of systems differing in the substrate composition were determined. The phase composition of synthesis products was determined by means of XRD analysis combined with Rietveld's method. The density of the obtained materials was determined by the Archimedes method. SEM observations enabled microstructures and homogeneity of sinters to be compared.On the basis of the conducted research it was found that using oxide additives containing magnesium cations allows the synthesis efficiency exceeding 95% as early as at the temperature of characterized by a homogeneous microstructure with a lower number and a smaller size of microcracks. 相似文献
998.
Magdalena Lassinantti Gualtieri Elena Colombini Denia Mazzini Claudio Alboni Tiziano Manfredini Cristina Siligardi 《Journal of the European Ceramic Society》2018,38(16):5563-5568
Lightweight impermeable ceramic bodies were designed by combining pore templating and controlled viscous sintering through in-situ crystallization. Various amounts of limestone were added to a glass-fluxed low-temperature stoneware tile formulation. Closed porosity was created by decomposition of carbonates prior to sintering, thus leaving voids that were not completely filled by the viscous melt. The resulting oxides chemically modified the liquid phase and promoted the crystallization of β-wollastonite, diopside and anorthite. Hence, viscous sintering was affected. The addition of limestone brought on several advantages: the temperature of maximum sintering rate was decreased (<900?°C); the dimensional stability range was extended; the matrix was reinforced by newly-formed crystals that compensated for the global structure weakening evoked by increased porosity; an increase in whiteness was observed in concomitance to crystallization, reaching values only obtained when using zircon as opacifier (L*=87). 相似文献
999.
1000.
Magdalena Lassinantti Gualtieri Marcello RomagnoliAlessandro F. Gualtieri 《Journal of the European Ceramic Society》2011,31(5):673-685
This paper reports a systematic and comprehensive investigation of the effects of the starting mixture composition on the mineralogy and properties of porcelain stoneware tiles using mixture design and full quantitative phase analyses by the Rietveld method. Functional relationships between properties and the raw material mixture proportions were obtained and related to the mineralogical composition of the fired product. Mullite crystallisation depended on the chemical environment. Dissolved quartz mounted to 10 wt% of the dry body regardless on initial amount, indicating saturation of the surrounding melt. The paramount role of the amorphous content on the stoneware properties was disclosed quantitatively. Open porosity decreased with increasing amount of amorphous content, and consequently both the stain and wear resistance increased. The CIE-Lab colour parameters a* and b* increased with increased amorphous content due to interaction with surface iron in hematite. The mullite content increased wear resistance, thus supporting the mullite strengthening theory. 相似文献