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201.
Dr. Laura Castoldi Ester Maria Di Tommaso Dr. Marcus Reitti Barbara Gräfen Prof. Berit Olofsson 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(36):15642-15646
The iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E-alkenyl sulfides with complete chemo- and regioselectivity, as well as excellent stereoselectivity. The methodology displays high functional group tolerance and proceeds under mild and transition metal-free conditions without the need for excess substrate or reagents. Mercaptothiazoles could be vinylated under modified conditions, resulting in opposite stereoselectivity compared to previous reactions with vinyliodonium salts. Novel VBX reagents with substituted benziodoxolone cores were prepared, and improved reactivity was discovered with a dimethyl-substituted core. 相似文献
202.
Jorge Leganés Bayón Prof. Ana Sánchez-Migallón Prof. Ángel Díaz-Ortiz Dr. Carlos Alberto Castillo Dr. Inma Ballesteros-Yáñez Prof. Sonia Merino Prof. Ester Vázquez 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(71):17069-17080
Electromagnetically driven drug delivery systems stand out among stimulus-responsive materials due to their ability to release cargo on demand by remote stimulation, such as light, near infrared (NIR) or microwave (MW) radiation. MW-responsive soft materials, such as hydrogels, generally operate at 2.45 GHz frequencies, which usually involves rapid overheating of the scaffold and may affect tissue surrounding the target location. In contrast, 915 MHz MW penetrate deeper tissues and are less prone to induce rapid overheating. In order to circumvent these limitations, we present here for the first time a graphene-based hydrogel that is responsive to MW irradiation of ν=915 MHz. This system is a candidate soft scaffold to deliver a model hydrophobic drug. The graphene present in the hydrogel acts as a heat-sink and avoids overheating of the scaffold upon MW irradiation. In addition, the microwave trigger stimulates the in vitro delivery of the model drug, thus suggesting a remote and deep-penetrating means to deliver a drug from a delivery reservoir. Moreover, the MW-triggered release of drug was observed to be enhanced under acidic conditions, where the swelling state is maximum due to the swelling-induced pH-responsiveness of the hydrogel. The hybrid composite described here is a harmless means to deliver remotely a hydrophobic drug on demand with a MW source of 915 MHz. Potential use in biomedical applications were evaluated by cytotoxicity tests. 相似文献
203.
First Pre‐Functionalised Polymeric Aromatic Framework from Mononitrotetrakis(iodophenyl)methane and its Applications 下载免费PDF全文
Ester Verde‐Sesto Dr. Mercedes Pintado‐Sierra Prof. Avelino Corma Dr. Eva M. Maya Prof. Jose G. de la Campa Prof. Marta Iglesias Prof. Felix Sánchez 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(17):5111-5120
Starting from mononitrotetrakis(iodophenyl)methane as monomer, we report the preparation of the first pre‐functionalised porous aromatic frameworks (PAFs) and their application as supports for organometallic catalysts. Neutral coordinate imino‐pyridine Schiff base ( PAF‐NPy ) or chiral bis‐amino ( PAF‐NPro ) ligands were obtained by post‐synthetic treatment of PAF‐NH2 and treated with copper(I) or rhodium(I) to yield the corresponding supported transition‐metal catalysts. The as‐prepared PAF‐NN‐M catalysts exhibited activity and selectivity similar to that of the corresponding homogeneous catalysts and were easily removed from reaction media and recycled without loss of activity or selectivity. 相似文献
204.
Ester Giorgi Francesca Binacchi Carlo Marotta Damiano Cirri Chiara Gabbiani Alessandro Pratesi 《Molecules (Basel, Switzerland)》2023,28(1)
Although important progress has been made, cancer still remains a complex disease to treat. Serious side effects, the insurgence of resistance and poor selectivity are some of the problems associated with the classical metal-based anti-cancer therapies currently in clinical use. New treatment approaches are still needed to increase cancer patient survival without cancer recurrence. Herein, we reviewed two promising—at least in our opinion—new strategies to increase the efficacy of transition metal-based complexes. First, we considered the possibility of assembling two biologically active fragments containing different metal centres into the same molecule, thus obtaining a heterobimetallic complex. A critical comparison with the monometallic counterparts was done. The reviewed literature has been divided into two groups: the case of platinum; the case of gold. Secondly, the conjugation of metal-based complexes to a targeting moiety was discussed. Particularly, we highlighted some interesting examples of compounds targeting cancer cell organelles according to a third-order targeting approach, and complexes targeting the whole cancer cell, according to a second-order targeting strategy. 相似文献
205.
206.
Design of the First‐in‐Class,Highly Potent Irreversible Inhibitor Targeting the Menin‐MLL Protein–Protein Interaction 下载免费PDF全文
Dr. Shilin Xu Dr. Angelo Aguilar Dr. Tianfeng Xu Dr. Ke Zheng Dr. Liyue Huang Prof. Dr. Jeanne Stuckey Dr. Krishnapriya Chinnaswamy Dr. Denzil Bernard Dr. Ester Fernández‐Salas Dr. Liu Liu Dr. Mi Wang Donna McEachern Sally Przybranowski Caroline Foster Prof. Dr. Shaomeng Wang 《Angewandte Chemie (International ed. in English)》2018,57(6):1601-1605
The structure‐based design of M‐525 as the first‐in‐class, highly potent, irreversible small‐molecule inhibitor of the menin‐MLL interaction is presented. M‐525 targets cellular menin protein at sub‐nanomolar concentrations and achieves low nanomolar potencies in cell growth inhibition and in the suppression of MLL‐regulated gene expression in MLL leukemia cells. M‐525 demonstrates high cellular specificity over non‐MLL leukemia cells and is more than 30 times more potent than its corresponding reversible inhibitors. Mass spectrometric analysis and co‐crystal structure of M‐525 in complex with menin firmly establish its mode of action. A single administration of M‐525 effectively suppresses MLL‐regulated gene expression in tumor tissue. An efficient procedure was developed to synthesize M‐525. This study demonstrates that irreversible inhibition of menin may be a promising therapeutic strategy for MLL leukemia. 相似文献
207.
This work is based on the analysis of the influence of dispersing agents on the non-isothermal kinetics, thermomechanical behavior and dispersing action of PET/TiO2 nanocomposites. The influence of two montanic waxes and an amide wax used as dispersing agents in the nucleating effect of the nanoparticles is studied. The dispersing agents are the following: a) a partly saponified ester of montanic acids (PSEMA), b) an ester of montanic acids with multifunctional alcohols (MAWMA) and c) an amide wax based on N,N′-Bisstearoyl ethylenediamine (AW). The non-isothermal kinetics based on the Avrami method revealed that MAWMA and PSEMA favors the nucleating effect of the nanoparticles when are included in PET. Birefringence microscopy points out the good dispersing capacity of MAWMA and AW and the termomechanical analysis confirmed that the ester of montanic acids with multifunctional alcohols MAWMA shows the best dispersing properties and best promotes the nucleating effect of the TiO2 nanoparticles when used for PET/TiO2 nanocomposites production. 相似文献
208.
Ester Mariucci 《Statistical Inference for Stochastic Processes》2016,19(1):71-91
This paper establishes the global asymptotic equivalence, in the sense of the Le Cam \(\Delta \)-distance, between scalar diffusion models with unknown drift function and small variance on the one side, and nonparametric autoregressive models on the other side. The time horizon \(T\) is kept fixed and both the cases of discrete and continuous observation of the path are treated. We allow non constant diffusion coefficient, bounded but possibly tending to zero. The asymptotic equivalences are established by constructing explicit equivalence mappings. 相似文献
209.
Dr. Ester Álvarez-Benedicto Dr. Zeru Tian Dr. Sumanta Chatterjee Dr. Domenico Orlando Dr. Minjeong Kim Erick D. Guerrero Dr. Xu Wang Dr. Daniel J. Siegwart 《Angewandte Chemie (International ed. in English)》2023,62(44):e202310395
Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B-cell lymphoma (BL). However, the current method of CAR T cell production is complicated and expensive, requiring collection of patient blood to enrich the T cell population, ex vivo engineering/activation, and quality assessment before the patient can receive the treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) to produce CAR T cells in situ and bypass the extensive and laborious process currently used. Optimized Spleen SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, and CD4+ T cells in wild-type mice. Spleen SORT LNPs delivered Cre recombinase mRNA and CAR encoding mRNA to T cells in reporter mice and in a lymphoreplete B cell lymphoma model (respectively) after intravenous injection without the need for active targeting ligands. Moreover, in situ CAR T cells increased the overall survival of mice with a less aggressive form of B cell lymphoma. In addition, in situ transfected CAR T cells reduced tumor metastasis to the liver by increasing tumor infiltrating lymphocytes. Overall, these results offer a promising alternative method for CAR T cell production with pre-clinical potential to treat hematological malignancies. 相似文献
210.
Dr. Shobhan Mondal Ester Maria Di Tommaso Prof. Berit Olofsson 《Angewandte Chemie (International ed. in English)》2023,62(8):e202216296
Efficient protocols for accessing iodo-substituted diaryl and aryl(vinyl) sulfides have been developed using iodonium salts as reactive electrophilic arylation and vinylation reagents. The reactions take place under transition-metal-free conditions, employing odorless and convenient sulfur reagents. A wide variety of functional groups are tolerated in the S-diarylation, enabling the regioselective late-stage application of several heterocycles and drug molecules under mild reaction conditions. A novel S-difunctionalization pathway was discovered using vinyliodonium salts, which proceeds under additive-free reaction conditions and grants excellent stereoselectivity in the synthesis of aryl(vinyl) sulfides. A one-pot strategy combining transition-metal-free diarylation and subsequent reduction provided facile access to electron-rich thioanilines and a direct synthesis of a potential drug candidate derivative. The retained iodo group allows a wide array of further synthetic transformations. Mechanistic insights were elucidated by isolating the key intermediate, and the relevant energy profile was substantiated by DFT calculations. 相似文献