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91.
There has been an increasing interest in the use of gallium in anticancer activity. However, whether the uptakes of two species of transferrin, including digallium transferrin (Ga2‐Tf) and the C‐terminal monogallium transferrin (GaC‐Tf) by cells, are different is not well understood. In this work the mechanism of both species passing in and out K562 cells has been established by using 125I‐labeled transferrin. There were about (1.5±0.08)×105 binding sites per cell surface. Both Ga2‐Tf and GaC‐Tf were recycled to the cell exterior with a protracted endocytic cycle compared to apotransferrin (apoTf). The cycling time from the internalization to release was calculated about t1/2= (3.15±0.055) min for apoTf, t1/2= (4.69±0.09) min for Ga2‐Tf and t1/2= (4.78±0.15) min for GaC‐Tf. The result implies that metal dissociating from transferrin in acidic endosomes was likely to be the key step. Both Ga2‐Tf and GaC‐Tf into K562 cells are transferrin receptor‐mediated process with a similar rate of endocytosis and release. Our present observations provide useful information for better targeted drugs in specific therapy. 相似文献
92.
93.
Dr. Xin Fang Ying Tong Di Yu Zhang Dr. Zhi Ping Xu Prof. Yang Lu Qian Qian Chen Prof. Qi Tai Zheng Prof. Dr. Xiao Jiang Hao 《Angewandte Chemie (International ed. in English)》2015,54(19):5592-5595
Perforalactone A ( 1 ), a new 20S quassinoid with a unique cagelike 2,4‐dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X‐ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid‐type natural products are also discussed. 相似文献
94.
Membrane receptors control fundamental cellular processes. Binding of a specific ligand to a receptor initiates communication through the membrane and activation of signaling cascades. This activation process often leads to a spatial rearrangement of receptors in the membrane at the molecular level. Single‐molecule techniques contributed significantly to the understanding of receptor organization and rearrangement in membranes. Here, we review four prominent single‐molecule techniques that have been applied to membrane receptors, namely, stepwise photobleaching, Förster resonance energy transfer, sub‐diffraction localization microscopy and co‐tracking. We discuss the requirements, benefits and limitations of each technique, discuss target labeling, present a selection of applications and results and compare the different methodologies. 相似文献
95.
Dr. Yong Zhang Dr. Huafei Zou Dr. Ying Wang Dawna Caballero Jose Gonzalez Elizabeth Chao Gus Welzel Dr. Weijun Shen Dr. Danling Wang Dr. Peter G. Schultz Dr. Feng Wang 《Angewandte Chemie (International ed. in English)》2015,54(7):2126-2130
Bovine antibody BLV1H12 possesses a unique “stalk–knob” architecture in its ultralong heavy chain CDR3, allowing substitutions of the “knob” domain with protein agonists to generate functional antibody chimeras. We have generated a humanized glucagon‐like peptide‐1 (GLP‐1) receptor agonist antibody by first introducing a coiled‐coil “stalk” into CDR3H of the antibody herceptin. Exendin‐4 (Ex‐4), a GLP‐1 receptor agonist, was then fused to the engineered stalk with flexible linkers, and a Factor Xa cleavage site was inserted immediately in front of Ex‐4 to allow release of the N‐terminus of the fused peptide. The resulting clipped herceptin–Ex‐4 fusion protein is more potent in vitro in activating GLP‐1 receptors than the Ex‐4 peptide. The clipped herceptin–Ex‐4 has an extended plasma half‐life of approximately four days and sustained control of blood glucose levels for more than a week in mice. This work provides a novel approach to the development of human or humanized agonist antibodies as therapeutics. 相似文献
96.
Water‐Soluble Molecularly Imprinted Nanoparticles (MINPs) with Tailored,Functionalized, Modifiable Binding Pockets
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Joseph K. Awino Prof. Dr. Yan Zhao 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(2):655-661
Construction of receptors with binding sites of specific size, shape, and functional groups is important to both chemistry and biology. Covalent imprinting of a photocleavable template within surface–core doubly cross‐linked micelles yielded carboxylic acid‐containing hydrophobic pockets within the water‐soluble molecularly imprinted nanoparticles. The functionalized binding pockets were characterized by their binding of amine‐ and acid‐functionalized guests under different pH values. The nanoparticles, on average, contained one binding site per particle and displayed highly selective binding among structural analogues. The binding sites could be modified further by covalent chemistry to modulate their binding properties. 相似文献
97.
Antiviral Activity of Synthetic Aminopyrrolic Carbohydrate Binding Agents: Targeting the Glycans of Viral gp120 to Inhibit HIV Entry
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Dr. Oscar Francesconi Prof. Cristina Nativi Dr. Gabriele Gabrielli Irene De Simone Sam Noppen Prof. Jan Balzarini Prof. Sandra Liekens Dr. Stefano Roelens 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(28):10089-10093
The binding abilities of a set of structurally related aminopyrrolic synthetic receptors for mannosides, endowed with antimycotic activity against yeast and yeast‐like pathogens bearing mannoproteins on their cell surface, have been investigated towards the highly mannosylated gp120 and gp41 glycoproteins of the HIV envelope. A pronounced binding interaction with both glycoproteins was observed by SPR for most of the investigated compounds. Comparison of their binding properties towards the glycoproteins with their binding affinities toward mannosides revealed a direct correlation, supporting their role as carbohydrate binding agents (CBAs). Cytostatic activity studies revealed antiproliferative activity dependent on the nature and the structure of compounds. Antiviral activity studies against a broad panel of DNA and RNA viruses showed inhibitory effect against HIV infection of the T‐lymphocyte CEM cell line for two compounds, suggesting antiviral activity similar to other CBAs, such as the nonpeptidic pradimicin antibiotics. 相似文献
98.
Cleavage of a PN Bond in a Urea‐Containing (Ph2P(R)PPh2)‐Bridged Dinuclear Gold(I) Thiolate Complex by Fluoride and a Mechanistic Insight
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Dr. Xiaoming He Dr. Wai Han Lam Dr. Eddie Chung‐Chin Cheng Prof. Dr. Vivian Wing‐Wah Yam 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(23):8447-8454
A urea‐containing, (Ph2P(R)PPh2)‐bridged, dinuclear, gold(I) thiolate complex, [Au2{Ph2PN(C6H4OMe‐4)PPh2}(SC6H4NHCONHC6H5)2] ( 1 ) was designed and synthesized and its photophysical and anion recognition properties studied. The results show that 1 has a high selectivity toward F?. Upon addition of F?, the yellow solution was decolorized, and drastic changes of emission and 1H and 31P{1H} NMR signals were observed. Interestingly, these changes are attributed to fluoride‐assisted P?N bond hydrolysis, instead of the expected hydrogen‐bonding interactions with the urea receptor. Similar changes were observed for two other basic anions, AcO? and H2PO4?, but to a much lesser extent; and these anions were found to bind to the urea receptor at the same time. On the other hand, Cl? was found to only bind to the urea moiety through hydrogen‐bonding interactions. Further studies with the control complex [Au2{Ph2PN(C6H4OMe‐4)PPh2}Cl2] ( 2 ) indicate that F? assists the hydrolysis process via cleavage of the P?N bond. DFT calculations were performed to study the reaction mechanism for the fluoride‐assisted P?N bond hydrolysis of 2 ; these provide a better insight into the role of fluoride in the hydrolysis. 相似文献
99.
Design,synthesis and insecticidal activities of novel anthranilic diamides containing polyfluoroalkyl pyrazole moiety 总被引:1,自引:0,他引:1
Jian-Jun Shi Gui-Hua Ren Ning-Jie Wu Jian-Quan Weng Tian-Ming Xu Xing-Hai Liu Cheng-Xia Tan 《中国化学快报》2017,28(8):1727-1730
In order to discover new molecules with good insecticidal activities, a series of anthranilic diamides containing polyfluoroalkyl pyrazole were designed and synthesized, and their structures were characterized by 1H NMR and HRMS. Bioassays demonstrated that some of the title compound exhibited excellent insecticidal activities. The larvicidal activities of compound 8a, 8c, 8g, 8k and 8l against Mythimna separata Walker were 100% at 0.8 mg/L. The insecticidal activities of compound 8a, 8c, 8e, 8g, 8k and 8l against Plutella xylostella Linnaeus were 100% at 0.4 mg/L. Surprisingly compounds 8a and 8c still showed 100% larvicidal activities against Plutella xylostella Linnaeus at 0.08 mg/L comparable to the commercialized Chlorantraniliprole. The LC50 of compound 8a and 8c against M. separata is 0.048 and 0.043 mg/L respectively. 相似文献
100.
《Angewandte Chemie (International ed. in English)》2017,56(47):15020-15024
A carbonaceous dumbbell was able to spontaneously glue two tubular receptors to form a unique two‐wheeled composite through van der Waals interactions, thus forcing the wheel components into contact with each other at the edges. In the present study, two tubular receptors with enantiomeric carbon networks were assembled on the dumbbell joint, and the handedness of the receptors was discriminated, thus leading to the self‐sorting of homomeric receptors from a mixture of enantiomeric tubes. The crystal structures of the composites revealed the structural origins of the molecular recognition driven by van der Waals forces as well as the presence of a columnar array of C120 molecules in a 1:1 composite. 相似文献