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601.
Kristen L. Huber Jos R. Fernndez Corey Webb Karl Rouzard Jason Healy Masanori Tamura Jeffry B. Stock Maxwell Stock Eduardo Prez 《Molecules (Basel, Switzerland)》2021,26(21)
Environmental stimuli attack the skin daily resulting in the generation of reactive oxygen species (ROS) and inflammation. One pathway that regulates oxidative stress in skin involves Protein Phosphatase 2A (PP2A), a phosphatase which has been previously linked to Alzheimer’s Disease and aging. Oxidative stress decreases PP2A methylation in normal human dermal fibroblasts (NHDFs). Thus, we hypothesize agents that increase PP2A methylation and activity will promote skin health and combat aging. To discover novel inhibitors of PP2A demethylation activity, we screened a library of 32 natural botanical extracts. We discovered Grape Seed Extract (GSE), which has previously been reported to have several benefits for skin, to be the most potent PP2A demethylating extract. Via several fractionation and extraction steps we developed a novel grape seed extract called Activated Grape Seed Extract (AGSE), which is enriched for PP2A activating flavonoids that increase potency in preventing PP2A demethylation when compared to commercial GSE. We then determined that 1% AGSE and 1% commercial GSE exhibit distinct gene expression profiles when topically applied to a 3D human skin model. To begin to characterize AGSE’s activity, we investigated its antioxidant potential and demonstrate it reduces ROS levels in NHDFs and cell-free assays equal to or better than Vitamin C and E. Moreover, AGSE shows anti-inflammatory properties, dose-dependently inhibiting UVA, UVB and chemical-induced inflammation. These results demonstrate AGSE is a novel, multi-functional extract that modulates methylation levels of PP2A and supports the hypothesis of PP2A as a master regulator for oxidative stress signaling and aging in skin. 相似文献
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603.
Brian H. Kaye David Alliet Laurie Switzer Cherie Turbitt-Daoust 《Particle & Particle Systems Characterization》1999,16(6):266-272
In an aerosol spectrometer the size of a powder grain is measured from the time-of-flight of the fineparticle between two laser beams. Due to the flow conditions, irregularly shaped fineparticles align themselves along the direction of flow of the air stream carrying them across the gap between the laser beams. The size distribution measured therefore varies with the shape of the fineparticles. This fact is demonstrated by comparing size distributions generated by image analysis, electrozone stream counter, diffractometer, and time-of-flight aerosol spectrometer. 相似文献
604.
E. J. Corey Weidong Li Tohru Nagamitsu 《Angewandte Chemie (International ed. in English)》1998,37(12):1676-1679
A selective, irreversible inhibitor of proteasome function , lactacystin ( 1 ) is an important experimental tool in cell biology. An efficient and direct enantioselective synthesis of lactacystin proceeds via the intermediates shown below. This process allows for the first time easy access to analogues of lactacystin in which the isopropyl substituent is replaced by other lipophilic groups. PMB=p-methoxybenzyl. 相似文献
605.
Elias J. Corey Christopher J. Helal 《Angewandte Chemie (International ed. in English)》1998,37(15):1986-2012
High enantioselectivity can be achieved when chiral oxazaborolidines are used as catalysts in the reduction of ketones by borane. In the transition state on the way to the complex chiral compounds, the two reactants are activated and held in close proximity by the catalyst, as shown below. 相似文献
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608.
Kyoung Chul Park Prof. Dr. Preecha Kittikhunnatham Dr. Jaewoong Lim Grace C. Thaggard Yuan Liu Dr. Corey R. Martin Dr. Gabrielle A. Leith Donald J. Toler Dr. An T. Ta Dr. Nancy Birkner Dr. Ingrid Lehman-Andino Dr. Alejandra Hernandez-Jimenez Dr. Gregory Morrison Dr. Jake W. Amoroso Prof. Dr. Hans-Conrad zur Loye Dr. Dave P. DiPrete Dr. Mark D. Smith Prof. Dr. Kyle S. Brinkman Prof. Dr. Simon R. Phillpot Prof. Dr. Natalia B. Shustova 《Angewandte Chemie (International ed. in English)》2023,62(5):e202216349
A novel series of heterometallic f-block-frameworks including the first examples of transuranic heterometallic 238U/239Pu-metal–organic frameworks (MOFs) and a novel monometallic 239Pu-analog are reported. In combination with theoretical calculations, we probed the kinetics and thermodynamics of heterometallic actinide(An)-MOF formation and reported the first value of a U-to-Th transmetallation rate. We concluded that formation of uranyl species could be a driving force for solid-state metathesis. Density of states near the Fermi edge, enthalpy of formation, band gap, proton affinity, and thermal/chemical stability were probed as a function of metal ratios. Furthermore, we achieved 97 % of the theoretical maximum capacity for An-integration. These studies shed light on fundamental aspects of actinide chemistry and also foreshadow avenues for the development of emerging classes of An-containing materials, including radioisotope thermoelectric generators or metalloradiopharmaceuticals. 相似文献
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610.
Dr. Alexandra C. Sun Dr. Daniel J. Steyer Dr. Richard I. Robinson Carol Ginsburg-Moraff Dr. Scott Plummer Dr. Jinhai Gao Dr. Joseph W. Tucker Dr. Dirk Alpers Prof. Corey R. J. Stephenson Prof. Robert T. Kennedy 《Angewandte Chemie (International ed. in English)》2023,62(28):e202301664
Within the realm of drug discovery, high-throughput experimentation techniques enable the rapid optimization of reactions and expedited generation of drug compound libraries for biological and pharmacokinetic evaluation. Herein we report the development of a segmented flow mass spectrometry-based platform to enable the rapid exploration of photoredox reactions for early-stage drug discovery. Specifically, microwell plate-based photochemical reaction screens were reformatted to segmented flow format to enable delivery to nanoelectrospray ionization-mass spectrometry analysis. This approach was demonstrated for the late-stage modification of complex drug scaffolds, as well as the subsequent structure–activity relationship evaluation of synthesized analogs. This technology is anticipated to expand the robust capabilities of photoredox catalysis in drug discovery by enabling high-throughput library diversification. 相似文献