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11.
Protein misfolding and aggregation are the hallmarks of many devastating diseases. We have previously shown that cyclic d,l-α-peptide CP-2 reacts and stabilizes less toxic forms of amyloid β (Aβ), and protects the cells from Aβ-induced toxicity. Here, we performed extensive structure-based studies on CP-2 to elucidate the contribution of each residue to the total antiamyloidogenic activity and determine the interactions that are involved between CP-2 and Aβ. We showed that the hydrophobicity of CP-2 analogs correlates with their antiamyloidogenic potency, however, aromatic interactions are even more important for this activity. The antiamyloidogenic activity of CP-2 analogs also correlates with their ability to self-assemble, as shown by the critical micelle concentration measurements. The cell survival studies performed on rat pheochromocytoma PC-12 cells suggest that incorporation of an additional aromatic residue to the CP-2's sequence increases its protective effect against Aβ42-induced toxicity. 相似文献
12.
Malte Behrends Charlotta Wallinder Anna Wieckowska Marie-Odile Guimond Anders Hallberg Nicole Gallo-Payet Mats Larhed 《ChemistryOpen》2014,3(2):65-75
A novel series of ligands for the recombinant human AT2 receptor has been synthesized utilizing a fast and efficient palladium-catalyzed procedure for aminocarbonylation as the key reaction. Molybdenum hexacarbonyl [Mo(CO)6] was employed as the carbon monoxide source, and controlled microwave heating was applied. The prepared N-aryl isoleucine derivatives, encompassing a variety of amide groups attached to the aromatic system, exhibit binding affinities at best with Ki values in the low micromolar range versus the recombinant human AT2 receptor. Some of the new nonpeptidic isoleucine derivatives may serve as starting points for further structural optimization. The presented data emphasize the importance of using human receptors in drug discovery programs. 相似文献
13.
Michele Tomasini Dr. Lucia Caporaso Jonathan Trouvé Dr. Jordi Poater Dr. Rafael Gramage-Doria Dr. Albert Poater 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(57):e202201970
Non-biological catalysts following the governing principles of enzymes are attractive systems to disclose unprecedented reactivities. Most of those existing catalysts feature an adaptable molecular recognition site for substrate binding that are prone to undergo conformational selection pathways. Herein, we present a non-biological catalyst that is able to bind substrates via the induced fit model according to in-depth computational calculations. The system, which is constituted by an inflexible substrate-recognition site derived from a zinc-porphyrin in the second coordination sphere, features destabilization of ground states as well as stabilization of transition states for the relevant iridium-catalyzed C−H bond borylation of pyridine. In addition, this catalyst appears to be most suited to tightly bind the transition state rather than the substrate. Besides these features, which are reminiscent of the action modes of enzymes, new elementary catalytic steps (i. e. C−B bond formation and catalyst regeneration) have been disclosed owing to the unique distortions encountered in the different intermediates and transition states. 相似文献
14.
We have developed an in-situ method using sonication (3 mm probe sonicator, 30 W, 20 kHz) and auto-reduction (control) to study the mechanism of the formation of manganese dioxide (MnO2) on a solid template (silk film), and its resulting enzymatic activity on tetramethylbenzidine (TMB) substrate. The fabrication of the silk film was first optimized for stability (no degradation) and optical transparency. A factorial approach was used to assess the effect of sonication time and the initial concentration of potassium permanganate (KMnO4). The result indicated a significant correlation with a fraction of KMnO4 consumed and MnO2 formation. Further, we found that the optimal process conditions to obtain a stable silk film with highly catalytic MnO2 nanoparticles (NPs) was 30 min of sonication in the presence of 0.5 mM of KMnO4 at a temperature of 20–24 °C. Under the optimal condition, we monitored in-situ the formation of MnO2 on the silk film, and after thorough rinsing, the in-situ catalysis of 0.8 mM of TMB substrate. For control, we used the auto-reduction of KMnO4 onto the silk film after about 16 h. The result from single-wavelength analysis confirmed the different kinetics rates for the formation of MnO2 via sonication and auto-reduction. The result from the multivariate component analysis indicated a three components route for sonication and auto-reduction to form MnO2-Silk. Overall, we found that the smaller size, more mono-dispersed, and deeper buried MnO2 NPs in silk film prepared by sonication, conferred a higher catalytic activity and stability to the hybrid material. 相似文献
15.
A Fluorescent Sensor for Dual‐Channel Discrimination between Phosgene and a Nerve‐Gas Mimic 下载免费PDF全文
Dr. Xin Zhou Yiying Zeng Chen Liyan Prof. Xue Wu Prof. Juyoung Yoon 《Angewandte Chemie (International ed. in English)》2016,55(15):4729-4733
The ability to analyze highly toxic chemical warfare agents (CWAs) and related chemicals in a rapid and precise manner is essential in order to alleviate serious threats to humankind and public security caused by unexpected terrorist attacks and industrial accidents. In this investigation, we designed a o‐phenylenediamine‐pyronin linked dye that is capable of both fluorogenic and colorimetric discrimination between phosgene and the prototypical nerve‐agent mimic, diethyl chlorophosphate (DCP) in the solution or gas phase. Moreover, this dye has been used to construct a portable kit that can be employed for real‐time monitoring of DCP and phosgene in the field, both in a discriminatory manner, and in a simple and safe way. 相似文献
16.
Enhanced Peroxidase‐Like Properties of Graphene–Hemin‐Composite Decorated with Au Nanoflowers as Electrochemical Aptamer Biosensor for the Detection of K562 Leukemia Cancer Cells 下载免费PDF全文
Dr. Jing Liu Meirong Cui Dr. Li Niu Dr. Hong Zhou Prof. Dr. Shusheng Zhang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(50):18001-18008
Graphene composites with hemin and gold nanoparticles show a better performance for hydrogen peroxide decomposition compared to that of the three components alone or duplex/hybrid complexes. Our previous studies showed that the morphology of the Au nanoparticles may greatly influence the catalytic activity of graphene‐family peroxidase mimics. Recently, we found that Au nanoflowers could grow in situ and form on the surface of hemin/RGO (reduced graphene oxide). The prickly morphology of this Au nanoflower brought a higher catalytic ability with enhanced kinetic parameters than traditional Au nanoparticles that showed a smooth surface. Therefore, based on this discovery, a smart electrochemical aptamer biosensor for K562 leukemia cancer cells was further presented with good performance in selectivity and sensitivity attributed to the excellent mimetic peroxidase catalytic activity of this newly synthesized Au nanoflower decorated graphene–hemin composite (H‐RGO‐Au NFs). 相似文献
17.
Kenji Mori Shigefumi Kuwahara Mitsuhiko Fujiwhara 《Journal of Chemical Sciences》1988,100(2-3):113-117
A mixture of the four stereoisomers of 2.6-dimethyloctyl formate was synthesized, and found to be a potent mimic of (4R,8R)-4,8-dimethyldecanal, the aggregation pheromone of the flour beetles,Tribolium castaneum andTribolium confusum.
For Part CVI, see Mori K and Puapoomchareon P 1988Liebigs Ann. Chem. 175 相似文献
18.
Tomáš Šmejkal Denis Gribkov Jens Geier Manfred Keller Bernhard Breit 《Chemistry (Weinheim an der Bergstrasse, Germany)》2010,16(8):2470-2478
A library of monodentate phosphane ligands, each bearing a guanidine receptor unit for carboxylates, was designed. Screening of the library gave some excellent catalysts for regioselective hydroformylation of β,γ‐unsaturated carboxylic acids. A terminal alkene, but‐3‐enoic acid, was hydroformylated with a linear/branched (l/b) regioselectivity up to 41. An internal alkene, pent‐3‐enoic acid was hydroformylated with regioselectivity up to 18:1. Further substrate selectivity (e.g., acid vs. methyl ester) and reaction site selectivity (monofunctionalization of 2‐vinylhept‐2‐enoic acid) were also achieved. Exploration of the structure–activity relationship and a practical and theoretical mechanistic study gave us an insight into the nature of the supramolecular guanidinium–carboxylate interaction within the catalytic system. This allowed us to identify a selective transition‐state stabilization by a secondary substrate–ligand interaction as the basis for catalyst activity and selectivity. 相似文献
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