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61.
Chenlin Feng Xuesong Wang Willem Jespers Rongfang Liu Sofía Denise Zamarbide Losada Marina Gorostiola Gonzlez Gerard J. P. van Westen Erik H. J. Danen Laura H. Heitman 《Molecules (Basel, Switzerland)》2022,27(15)
The adenosine A2A receptor (A2AAR) is a class A G-protein-coupled receptor (GPCR). It is an immune checkpoint in the tumor micro-environment and has become an emerging target for cancer treatment. In this study, we aimed to explore the effects of cancer-patient-derived A2AAR mutations on ligand binding and receptor functions. The wild-type A2AAR and 15 mutants identified by Genomic Data Commons (GDC) in human cancers were expressed in HEK293T cells. Firstly, we found that the binding affinity for agonist NECA was decreased in six mutants but increased for the V275A mutant. Mutations A165V and A265V decreased the binding affinity for antagonist ZM241385. Secondly, we found that the potency of NECA (EC50) in an impedance-based cell-morphology assay was mostly correlated with the binding affinity for the different mutants. Moreover, S132L and H278N were found to shift the A2AAR towards the inactive state. Importantly, we found that ZM241385 could not inhibit the activation of V275A and P285L stimulated by NECA. Taken together, the cancer-associated mutations of A2AAR modulated ligand binding and receptor functions. This study provides fundamental insights into the structure–activity relationship of the A2AAR and provides insights for A2AAR-related personalized treatment in cancer. 相似文献
62.
Dibyalochan Mohanty Ameeduzzafar Zafar Mohammed Jafar Atul Kumar Upadhyay Mohammad Akiful Haque Jeetendra Kumar Gupta Vasudha Bakshi Mohammed M. Ghoneim Sultan Alshehri Mohammed Asadullah Jahangir Mohammed Javed Ansari 《Molecules (Basel, Switzerland)》2022,27(9)
Objective: The present study aimed to develop and optimize esomeprazole loaded proniosomes (EZL-PNs) to improve bioavailability and therapeutic efficacy. Method: EZL-PNs formulation was developed by slurry method and optimized by 33 box-Bhekhen statistical design software. Span 60 (surfactant), cholesterol, EZL concentration were taken as independent variables and their effects were evaluated on vesicle size (nm), entrapment efficiency (%, EE) and drug release (%, DR). Furthermore, optimized EZL-PNs (EZL-PNs-opt) formulation was evaluated for ex vivo permeation, pharmacokinetic and ulcer protection activity. Result: The EZL-PNs-opt formulation showed 616 ± 13.21 nm of vesicle size, and 81.21 ± 2.35% of EE. EZL-PNs-opt exhibited negative zeta potential and spherical confirmed scanning electron microscopy. EZL-PNs-opt showed sustained release of EZL (95.07 ± 2.10% in 12 h) than pure EZL dispersion. The ex-vivo gut permeation result exhibited a significantly (p < 0.05) enhanced flux than pure EZL. The in vivo results revealed 4.02-fold enhancement in bioavailability and 61.65% protection in ulcer than pure EZL dispersion (43.82%). Conclusion: Our findings revealed that EZL-PNs formulation could be an alternative delivery system of EZL to enhance oral bioavailability and antiulcer activity. 相似文献
63.
Micha Juszczak Magdalena Kluska Aneta Kosiska Bogna Rudolf Katarzyna Wo
niak 《Molecules (Basel, Switzerland)》2022,27(9)
In these studies, we investigated the antioxidant activity of three ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η5-cyclopentadienyl)Ru(CO)2-N-methoxysuccinimidato (1), (η5-cyclopentadienyl)Ru(CO)2-N-ethoxysuccinimidato (2), and (η5-cyclopentadienyl)Ru(CO)2-N-phthalimidato (3). We studied the effects of ruthenium complexes 1–3 at a low concentration of 50 µM on the viability and the cell cycle of peripheral blood mononuclear cells (PBMCs) and HL-60 leukemic cells exposed to oxidative stress induced by hydrogen peroxide (H2O2). Moreover, we examined the influence of these complexes on DNA oxidative damage, the level of reactive oxygen species (ROS), and superoxide dismutase (SOD) activity. We have observed that ruthenium complexes 1–3 increase the viability of both normal and cancer cells decreased by H2O2 and also alter the HL-60 cell cycle arrested by H2O2 in the sub-G1 phase. In addition, we have shown that ruthenium complexes reduce the levels of ROS and oxidative DNA damage in both cell types. They also restore SOD activity reduced by H2O2. Our results indicate that ruthenium complexes 1–3 bearing succinimidato and phthalimidato ligands have antioxidant activity without cytotoxic effect at low concentrations. For this reason, the ruthenium complexes studied by us should be considered interesting molecules with clinical potential that require further detailed research. 相似文献
64.
Rana M. El-Masry Hanan H. Kadry Azza T. Taher Sahar M. Abou-Seri 《Molecules (Basel, Switzerland)》2022,27(9)
The bioisosteres of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles are well-known pharmacophores for many medicinally important drugs. Throughout the past 10 years, 1,3,4-oxa-/thiadiazole nuclei have been very attractive to researchers for drug design, synthesis, and the study of their potential activity towards a variety of diseases, including microbial and viral infections, cancer, diabetes, pain, and inflammation. This work is an up-to-date comparative study that identifies the differences between 1,3,4-thiadiazoles and 1,3,4-oxadiazoles concerning their methods of synthesis from different classes of starting compounds under various reaction conditions, as well as their biological activities and structure–activity relationship. 相似文献
65.
Sarra Akermi Slim Smaoui Khaoula Elhadef Mariam Fourati Nacim Louhichi Moufida Chaari Ahlem Chakchouk Mtibaa Aissette Baanannou Saber Masmoudi Lotfi Mellouli 《Molecules (Basel, Switzerland)》2022,27(9)
Nowadays, increasing interest has recently been given to the exploration of new food preservatives to avoid foodborne outbreaks or food spoilage. Likewise, new compounds that substitute the commonly used synthetic food preservatives are required to restrain the rising problem of microbial resistance. Accordingly, the present study was conducted to examine the chemical composition and the mechanism(s) of action of the Cupressus sempervirens essential oil (CSEO) against Salmonella enterica Typhimuriumand Staphyloccocus aureus. The gas chromatography analysis revealed α-pinene (38.47%) and δ-3-carene (25.14%) are the major components of the CSEO. By using computational methods, such as quantitative structure–activity relationship (QSAR), we revealed that many CSEO components had no toxic effects. Moreover, findings indicated that α-pinene, δ-3-carene and borneol, a minor compound of CSEO, could inhibit the AcrB-TolC and MepR efflux pump activity of S. enterica Typhimurium and S. aureus, respectively. In addition, our molecular docking predictions indicated the high affinity of these three compounds with active sites of bacterial DNA and RNA polymerases, pointing to plausible impairments of the pathogenic bacteria cell replication processes. As well, the safety profile was developed through the zebrafish model. The in vivo toxicological evaluation of (CSEO) exhibited a concentration-dependent manner, with a lethal concentration (LC50) equal to 6.6 µg/mL. 相似文献
66.
David E. Mery Amanda J. Compadre Paola E. Ordez Edward J. Selvik Vladimir Morocho Jorge Contreras Omar Malagn Darin E. Jones Philip J. Breen Michael J. Balick Flavio G. Gaudio Monica L. Guzman Cesar M. Compadre 《Molecules (Basel, Switzerland)》2022,27(9)
A method to identify anticancer compounds in plants was proposed based on the hypothesis that these compounds are primarily present in plants to provide them with an ecological advantage over neighboring plants and other competitors. According to this view, identifying plants that contain compounds that inhibit or interfere with the development of other plant species may facilitate the discovery of novel anticancer agents. The method was developed and tested using Magnolia grandiflora, Gynoxys verrucosa, Picradeniopsis oppositifolia, and Hedyosmum racemosum, which are plant species known to possess compounds with cytotoxic activities. Plant extracts were screened for growth inhibitory activity, and then a thin-layer chromatography bioautography assay was conducted. This located the major antileukemic compounds 1, 2, 4, and 5 in the extracts. Once the active compounds were located, they were extracted and purified, and their structures were determined. The growth inhibitory activity of the purified compounds showed a significant correlation with their antileukemic activity. The proposed approach is rapid, inexpensive, and can easily be implemented in areas of the world with high biodiversity but with less access to advanced facilities and biological assays. 相似文献
67.
M. S. Behalo A. A. Aly 《Phosphorus, sulfur, and silicon and the related elements》2013,188(11):2194-2200
A one-pot three component synthesis of alkyl/aryl-dithiocarbamic acid-3-oxo-3-(phenoxathiin-2-yl)-1-phenyl/(4-chlorophenyl)propyl esters (3a–n) was achieved from the reaction of 3-phenyl/(4-chlorophenyl)-1-(phenoxathiin-2-yl)propenones (1a,b), amine, and carbon disulfide. The antimicrobial activities of some compounds were also screened against some selected bacteria and fungi. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. 相似文献
68.
Z. H. Ismail M. M. Ghorab E. M. A. Mohamed H. M. Aly M. S. A. El-Gaby 《Phosphorus, sulfur, and silicon and the related elements》2013,188(10):2541-2554
Some novel thiourea,1,2,4-triazole, quinazoline, thieno[2,3-d]pyrimi-dine, and thiazolidine derivatives were synthesized to evaluate their antitumor activity. Compound (3f) is nearly as active as reference drug, (Doxorubicin) as positive control. 相似文献
69.
合成了一系列以两个亚甲基为联接基的杂双子咪唑表面活性剂([Cm-2-Cnim]Br2, m, n=8, 10, 12, 14, 16; m≠n). 用氢谱和质谱对其结构进行了表征. 探索了物料比、反应温度和时间对反应产率的影响. 对合成的杂双子咪唑表面活性剂的表面活性进行了研究,讨论了分子结构的不对称程度对表面活性的影响. 相似文献
70.
《Physics and Chemistry of Liquids》2012,50(4):345-349
Abstract Isobaric vapour-liquid equilibrium data are measured at 200, 500 and 707 mm Hg at ten compositions spread evenly over the entire liquid mole fraction range, employing a Swietoslawski type ebulliometer. The liquid phase composition vs. bubble temperature (x-t) data are found to be well represented by Wilson model The optimum Wilson parameters are used to calculate the vapour phase compositions, activity coefficients and the excess Gibbs free energies. 相似文献