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961.
962.
《Journal of mass spectrometry : JMS》2017,52(7):ii-ii
Conformational change and modification of proteins are involved in many cellular functions. However, they can also have adverse effects that are implicated in numerous diseases. How structural change promotes disease is generally not well‐understood. This perspective illustrates how mass spectrometry (MS), followed by toxicological and epidemiological validation, can discover disease‐relevant structural changes and therapeutic strategies. We (with our collaborators) set out to characterize the structural and toxic consequences of disease‐associated mutations and post‐translational modifications (PTMs) of the cytosolic antioxidant protein Cu/Zn‐superoxide dismutase (SOD1). Previous genetic studies discovered >180 different mutations in the SOD1 gene that caused familial (inherited) amyotrophic lateral sclerosis (fALS). Using hydrogen–deuterium exchange with mass spectrometry, we determined that diverse disease‐associated SOD1 mutations cause a common structural defect – perturbation of the SOD1 electrostatic loop. X‐ray crystallographic studies had demonstrated that this leads to protein aggregation through a specific interaction between the electrostatic loop and an exposed beta‐barrel edge strand. Using epidemiology methods, we then determined that decreased SOD1 stability and increased protein aggregation are powerful risk factors for fALS progression, with a combined hazard ratio > 300 (for comparison, a lifetime of smoking is associated with a hazard ratio of ~15 for lung cancer). The resulting structural model of fALS etiology supported the hypothesis that some sporadic ALS (sALS, ~80% of ALS is not associated with a gene defect) could be caused by post‐translational protein modification of wild‐type SOD1. We developed immunocapture antibodies and high sensitivity top‐down MS methods and characterized PTMs of wild‐type SOD1 using human tissue samples. Using global hydrogen–deuterium exchange, X‐ray crystallography and neurotoxicology, we then characterized toxic and protective subsets of SOD1 PTMs. To cap this perspective, we present proof‐of‐concept that post‐translational modification can cause disease. We show that numerous mutations (N➔D; Q➔E), which result in the same chemical structure as the PTM deamidation, cause multiple diseases. Copyright © 2017 John Wiley & Sons, Ltd. 相似文献
963.
《Angewandte Chemie (International ed. in English)》2017,56(16):4612-4616
The treatment of various N‐morpholino amides with TMPZnCl⋅LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) and Mg(OPiv)2 in THF at 25 °C provides solid zinc enolates with enhanced air and moisture stability (t 1/2 in air: 1–3 h) after solvent evaporation. These enolates undergo Pd‐ and Cu‐catalyzed cross‐couplings with (hetero)aryl bromides as well as allylic and benzylic halides. The arylated N‐morpholino amides were converted into various ketones by LaCl3⋅2 LiCl mediated acylation with Grignard reagents. The new, solid enolates were used to prepare a potent anti‐breast‐cancer drug candidate in six steps and 23 % overall yield. 相似文献
964.
《Angewandte Chemie (International ed. in English)》2017,56(33):9670-9679
During the last 40 years, researchers investigating photoinitiated cationic polymerizations have delivered tremendous success in both industrial and academic settings. A myriad of photoinitiating systems have been developed, thus allowing polymerization of a broad array of monomers (e.g., epoxides, vinyl ethers, alkenes, cyclic ethers, and lactones) under practical, inexpensive, and environmentally benign conditions. More recently, owing to progress in photoredox catalysis, photocontrolled cationic polymerization has emerged as a means to precisely regulate polymer chain growth. This Minireview provides a concise historical perspective on cationic polymerization induced by light and discusses the latest advances in both photoinitiated and photocontrolled processes. The latter are exciting new directions for the field that will likely impact industries ranging from micropatterning to the synthesis of complex biomaterials and sequence‐controlled polymers. 相似文献
965.
Alexander A. Kirichok Dr. Iryna Shton Dr. Maria Kliachyna Dr. Iryna Pishel Dr. Pavel K. Mykhailiuk 《Angewandte Chemie (International ed. in English)》2017,56(30):8865-8869
The 2-substituted piperidine core is found in drugs (18 FDA-approved drugs), however, their spirocyclic analogues remain unknown. Described here is the synthesis of spirocyclic analogues for 2-substituted piperidines and a demonstration of their validation in drug discovery. 相似文献
966.
Dr. Yifeng Chen David Huang Yizhou Zhao Prof. Dr. Timothy R. Newhouse 《Angewandte Chemie (International ed. in English)》2017,56(28):8258-8262
The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences. 相似文献
967.
《Journal of separation science》2017,40(17):3545-3556
A comparison of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography for the separation of synthetic cathinones has been conducted. Nine different mixtures of bath salts were analyzed in this study. The three different chromatographic techniques were examined using a general set of controlled synthetic cathinones as well as a variety of other synthetic cathinones that exist as positional isomers. Overall 35 different synthetic cathinones were analyzed. A variety of column types and chromatographic modes were examined for developing each separation. For the ultra high performance supercritical fluid chromatography separations, analyses were performed using a series of Torus and Trefoil columns with either ammonium formate or ammonium hydroxide as additives, and methanol, ethanol or isopropanol organic solvents as modifiers. Ultra high performance liquid chromatographic separations were performed in both reversed phase and hydrophilic interaction chromatographic modes using SPP C18 and SPP HILIC columns. Gas chromatography separations were performed using an Elite‐5MS capillary column. The orthogonality of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography was examined using principal component analysis. For the best overall separation of synthetic cathinones, the use of ultra high performance supercritical fluid chromatography in combination with gas chromatography is recommended. 相似文献
968.
《Macromolecular bioscience》2017,17(5)
Using colloidal polyacrylamide (PAAm) microgels as carriers, a novel strategy for covalent immobilization of enzymes maintained in hydrated microenvironment on/in a macroporous surface‐functionalized hydrophobic polyvinylidene fluoride (PVDF) membrane is developed. The PAAm microgels are synthesized by inverse miniemulsion polymerization, and first the parameters are investigated which are suited to obtain particles in the desired size range, 100–200 nm, with narrow size distribution. Amino functions are then imparted to the microgels applying the Hofmann reaction. The modification is confirmed by Fourier‐transform infrared spectroscopy analysis, ninhydrin test, and elemental analysis. In addition, functionalized microgels are characterized by dynamic light scattering. The amino‐functionalized PAAm microgels are then immobilized on pre‐modified PVDF membrane having aldehyde functionalities on the surface. Afterward, unreacted aldehyde groups still present on the membrane where quenched by ethanolamine and the enzyme lipase from Candida rugosa (LCR) is subsequently immobilized on the microgels loaded PVDF membrane via glutaraldehyde cross‐linking, exploiting the free amino groups on immobilized microgels. Catalytic efficiency of LCR immobilized by this strategy is evaluated using para‐nitrophenyl palmitate as substrate and compared with LCR directly immobilized on PVDF membrane without microgels. Results show that LCR immobilized by means of microgels exhibits better performance with a 2.3‐fold higher specific biocatalytic activity.
969.
单晶硅表面改性及其微观摩擦学性能研究进展 总被引:8,自引:2,他引:8
评述了单晶硅表面改性及其微观摩擦磨损性能研究现状和进展,就单晶硅微观机械性能和摩擦磨损性能、单晶硅表面沉积薄膜和氧化层的微观机械和摩擦学性能及硅材料表面离子注入和表面纳米化等相关研究进行了归纳总结;指出应当继续深化硅材料表面改性技术及改性层微观摩擦学性能的研究,特别是应当加强硅材料表面离子注入及表面纳米化的研究,从而满足MEMs/NEMs等高技术领域的应用和发展需要. 相似文献
970.
QixiangWang GuoqingNing FeiWei GuohuaLuo 《中国颗粒学报》2003,1(6):253-257
Multi-walled carbon nanotubes (MWNTs) with 20 nm outer diameter were prepared by chemical vapor deposition of ethylene using ultrafine surface-modified acicular α-Fe catalyst particles.The growth mechanism of MWNTs on the larger catalyst particles are attributed to the interaction between the Fe nanoparticles with the surface-modified silica layer.This interaction-mediated growth mechanism is illustrated by studying the electronic,atomic and crystal properties of surface-modified catalysts and MWNTs products by characterization with X-ray diffraction (XRD),transmission electron microscopy (TEM),high resolution transmission electron microscopy (HRTEM),thermal gravimetric analysis (TGA) and Raman spectra. 相似文献