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41.
Elbieta mudzka Klaudia Lustyk Agata Siwek Magorzata Wolak Adam Gauszka Jolanta Jakowska Marcin Koaczkowski Jacek Sapa Karolina Pytka 《International journal of molecular sciences》2023,24(1)
Cardiovascular diseases remain one of the leading causes of death worldwide. Unfortunately, the available pharmacotherapeutic options have limited effectiveness. Therefore, developing new drug candidates remains very important. We selected six novel arylpiperazine alkyl derivatives of salicylamide to investigate their cardiovascular effects. Having in mind the beneficial role of α1-adrenergic receptors in restoring sinus rhythm and regulating blood pressure, first, using radioligand binding assays, we evaluated the affinity of the tested compounds for α-adrenergic receptors. Our experiments revealed their high to moderate affinity for α1- but not α2-adrenoceptors. Next, we aimed to determine the antiarrhythmic potential of novel derivatives in rat models of arrhythmia induced by adrenaline, calcium chloride, or aconitine. All compounds showed potent prophylactic antiarrhythmic activity in the adrenaline-induced arrhythmia model and no effects in calcium chloride- or aconitine-induced arrhythmias. Moreover, the tested compounds demonstrated therapeutic antiarrhythmic activity, restoring a normal sinus rhythm immediately after the administration of the arrhythmogen adrenaline. Notably, none of the tested derivatives affected the normal electrocardiogram (ECG) parameters in rodents, which excludes their proarrhythmic potential. Finally, all tested compounds decreased blood pressure in normotensive rats and reversed the pressor response to methoxamine, suggesting that their hypotensive mechanism of action is connected with the blockade of α1-adrenoceptors. Our results confirm the antiarrhythmic and hypotensive activities of novel arylpiperazine derivatives and encourage their further investigation as model structures for potential drugs. 相似文献
42.
Thierbach S Büldt-Karentzopoulos K Dreiling A Hennecke U König S Fetzner S 《Chembiochem : a European journal of chemical biology》2012,13(8):1125-1127
Mechanistic promiscuity: The (2-alkyl)-3-hydroxy-4(1H)-quinolone-cleaving dioxygenase Hod has an α/β-hydrolase fold and a Ser/His/Asp triad in its active site. Isatoic anhydride, a suicide substrate of serine hydrolases, inactivates Hod by covalent modification of the active-site serine, thus indicating that the α/β-hydrolase fold can accommodate dioxygenase chemistry without completely abandoning hydrolase-like properties. 相似文献
43.
Dynamic light scattering represents a suitable method for measuring the thermal diffusivity of optically transparent fluids. The classic application of the method is the immediate vicinity around the critical point due to its dependence upon the intensity of scattered light and its high sensitivity to undesired light scattering. By means of subsequent modifications of the experimental setup, we have been able to expand this region of applicability over the last 12 years and could systematically investigate numerous substances and their binary mixtures within a temperature range of 280 K<T<350 K. Our planned investigation of fluids suitable for ORC-HP-technology necessitates performing measurements at higher temperatures and pressures. The experimental apparatus newly designed for this purpose is capable of sustaining a relatively high temperature constance at temperatures up to 700 K. Factors restricting the measurable range of state and their influence on the design of the sample cell are discussed.Paper presented at the Tenth Symposium on Thermophysical Properties, June 20–23, 1988, Gaithersburg, Maryland, U.S.A. 相似文献
44.
45.
Aleksandra Majewska Kinga Wilkus Klaudia Brodaczewska Claudine Kieda 《International journal of molecular sciences》2021,22(2)
Endothelial cells (ECs) lining the blood vessels are important players in many biological phenomena but are crucial in hypoxia-dependent diseases where their deregulation contributes to pathology. On the other hand, processes mediated by ECs, such as angiogenesis, vessel permeability, interactions with cells and factors circulating in the blood, maintain homeostasis of the organism. Understanding the diversity and heterogeneity of ECs in different tissues and during various biological processes is crucial in biomedical research to properly develop our knowledge on many diseases, including cancer. Here, we review the most important aspects related to ECs’ heterogeneity and list the available in vitro tools to study different angiogenesis-related pathologies. We focus on the relationship between functions of ECs and their organo-specificity but also point to how the microenvironment, mainly hypoxia, shapes their activity. We believe that taking into account the specific features of ECs that are relevant to the object of the study (organ or disease state), especially in a simplified in vitro setting, is important to truly depict the biology of endothelium and its consequences. This is possible in many instances with the use of proper in vitro tools as alternative methods to animal testing. 相似文献
46.
Jessica Mühlhaus Juliane Dinter Daniela Nürnberg Maren Rehders Maren Depke Janine Golchert Georg Homuth Chun-Xia Yi Silke Morin Josef K?hrle Klaudia Brix Matthias Tsch?p Gunnar Kleinau Heike Biebermann 《International journal of molecular sciences》2014,15(11):20638-20655
The thyroid hormone derivative 3-iodothyronamine (3-T1AM) exerts metabolic effects in vivo that contradict known effects of thyroid hormones. 3-T1AM acts as a trace amine-associated receptor 1 (TAAR1) agonist and activates Gs signaling in vitro. Interestingly, 3-T1AM-meditated in vivo effects persist in Taar1 knockout-mice indicating that further targets of 3-T1AM might exist. Here, we investigated another member of the TAAR family, the only scarcely studied mouse and human trace-amine-associated receptor 8 (Taar8b, TAAR8). By RT-qPCR and locked-nucleic-acid (LNA) in situ hybridization, Taar8b expression in different mouse tissues was analyzed. Functionally, we characterized TAAR8 and Taar8b with regard to cell surface expression and signaling via different G-protein-mediated pathways. Cell surface expression was verified by ELISA, and cAMP accumulation was quantified by AlphaScreen for detection of Gs and/or Gi/o signaling. Activation of G-proteins Gq/11 and G12/13 was analyzed by reporter gene assays. Expression analyses revealed at most marginal Taar8b expression and no gender differences for almost all analyzed tissues. In heart, LNA-in situ hybridization demonstrated the absence of Taar8b expression. We could not identify 3-T1AM as a ligand for TAAR8 and Taar8b, but both receptors were characterized by a basal Gi/o signaling activity, a so far unknown signaling pathway for TAARs. 相似文献
47.
Dominika Rozmus Janusz Pomiski Klaudia Augustyn Anna Cieliska 《International journal of molecular sciences》2022,23(2)
The purpose of the study was to investigate the role of vitamin D binding protein (VDBP, DBP) and its polymorphism in the vitamin D pathway and human health. This narrative review shows the latest literature on the most popular diseases that have previously been linked to VDBP. Vitamin D plays a crucial role in human metabolism, controlling phosphorus and calcium homeostasis. Vitamin D binding protein bonds vitamin D and its metabolites and transports them to target tissues. The most common polymorphisms in the VDBP gene are rs4588 and rs7041, which are located in exon 11 in domain III of the VDBP gene. rs4588 and rs7041 may be correlated with differences not only in vitamin D status in serum but also with vitamin D metabolites. This review supports the role of single nucleotide polymorphisms (SNPs) in the VDBP gene and presents the latest data showing correlations between VDBP variants with important human diseases such as obesity, diabetes mellitus, tuberculosis, chronic obstructive pulmonary disease, and others. In this review, we aim to systematize the knowledge regarding the occurrence of diseases and their relationship with vitamin D deficiencies, which may be caused by polymorphisms in the VDBP gene. Further research is required on the possible influence of SNPs, modifications in the structure of the binding protein, and their influence on the organism. It is also important to mention that most studies do not have a specific time of year to measure accurate vitamin D metabolite levels, which can be misleading in conclusions due to the seasonal nature of vitamin D. 相似文献
48.
Agnieszka Kosowska Wojciech Garczorz Agnieszka Kych-Ratuszny Mohammad Reza F. Aghdam Magorzata Kimsa-Furdzik Klaudia Simka-Lampa Tomasz Francuz 《International journal of molecular sciences》2020,21(23)
The strong association between diabetes mellitus type 2 and cancer is observed. The incidence of both diseases is increasing globally due to the interaction between them. Recent studies suggest that there is also an association between cancer incidence and anti-diabetic medications. An inhibitor of dipeptidyl-peptidase 4 (DPP-4), sitagliptin, is used in diabetes treatment. We examined the influence of sitagliptin alone or in combination with a cytostatic drug (paclitaxel) on the development of epithelial ovarian cancer cells and the process of metastasis. We examined migration, invasiveness, apoptosis, and metalloproteinases (MMPs) and their inhibitors’ (TIMPs) production in two human ovarian cancer cell lines. Sitagliptin induced apoptosis by caspase 3/7 activation in paclitaxel-treated SKOV-3 and OVCAR-3 cells. Sitagliptin maintained paclitaxel influence on ERK and Akt signaling pathways. Sitagliptin additionally reduced migration and invasiveness of SKOV-3 cells. There were distinct differences of metalloproteinases production in sitagliptin-stimulated ovarian cancer cells in both cell lines, despite their identical histological classification. Only the SKOV-3 cell line expressed MMPs and TIMPs. SKOV-3 cells co-treated with sitagliptin and paclitaxel decreased concentrations of MMP-1, MMP-2, MMP-7, MMP-10, TIMP-1, TIMP-2. The obtained data showed that sitagliptin used with paclitaxel may be considered as a possibility of pharmacological modulation of intracellular transmission pathways to improve the response to chemotherapy. 相似文献
49.
Andrew Nattestad Klaudia Wagner Gordon G. Wallace 《Frontiers of Chemical Science and Engineering》2023,17(1):116
In recent times there has been a great deal of interest in the conversion of carbon dioxide into more useful chemical compounds. On the other hand, the translation of these developments in electrochemical reduction of carbon dioxide from the laboratory bench to practical scale remains an underexplored topic. Here we examine some of the major challenges, demonstrating some promising strategies towards such scale-up, including increased electrode area and stacking of electrode pairs in different configurations. We observed that increasing the electrode area from 1 to 10 cm2 led to only a 4% drop in current density, with similarly small penalties realised when stacking sub-cells together. 相似文献
50.
Boos J.B. Kruppa W. Bennett B.R. Park D. Kirchoefer S.W. Bass R. Dietrich H.B. 《Electron Devices, IEEE Transactions on》1998,45(9):1869-1875
The design, fabrication, and characterization of 0.1 μm AlSb/InAs HEMT's are reported. These devices have an In0.4Al 0.6As/AlSb composite barrier above the InAs channel and a p + GaSb layer within the AlSb buffer layer. The HEMT's exhibit a transconductance of 600 mS/mm and an fT of 120 GHz at VDs=0.6 V. An intrinsic fT of 160 GHz is obtained after the gate bonding pad capacitance is removed from an equivalent circuit. The present HEMT's have a noise figure of 1 dB with 14 dB associated gain at 4 GHz and VDs=0.4 V. Noise equivalent circuit simulation indicates that this noise figure is primarily limited by gate leakage current and that a noise figure of 0.3 dB at 4 GHz is achievable with expected technological improvements. HEMT's with a 0.5 μm gate length on the same wafer exhibit a transconductance of 1 S/mm and an intrinsic fTLg, product of 50 GHz-μm 相似文献