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991.
Gertrud E. Morlock Julia Heil Valrie Bardot Loïc Lenoir Csar Cotte Michel Dubourdeaux 《Molecules (Basel, Switzerland)》2021,26(5)
An effect-directed profiling method was developed to investigate 17 different fortified plant extracts for potential benefits. Six planar effect-directed assays were piezoelectrically sprayed on the samples separated side-by-side by high-performance thin-layer chromatography. Multipotent compounds with antibacterial, α-glucosidase, β-glucosidase, AChE, tyrosinase and/or β-glucuronidase-inhibiting effects were detected in most fortified plant extracts. A comparatively high level of antimicrobial activity was observed for Eleutherococcus, hops, grape pomace, passiflora, rosemary and Eschscholzia. Except in red vine, black radish and horse tail, strong enzyme inhibiting compounds were also detected. Most plants with anti-α-glucosidase activity also inhibited β-glucosidase. Green tea, lemon balm and rosemary were identified as multipotent plants. Their multipotent compound zones were characterized by high-resolution mass spectrometry to be catechins, rosmarinic acid, chlorogenic acid and gallic acid. The results pointed to antibacterial and enzymatic effects that were not yet known for plants such as Eleutherococcus and for compounds such as cynaratriol and caffeine. The nontarget effect-directed profiling with multi-imaging is of high benefit for routine inspections, as it provides comprehensive information on the quality and safety of the plant extracts with respect to the global production chain. In this study, it not only confirmed what was expected, but also identified multipotent plants and compounds, and revealed new bioactivity effects. 相似文献
992.
Nadipolla Naresh Reddy Sung-Jen Hung Merugu Kumara Swamy Ananthula Sanjeev Vankadari Srinivasa Rao Rondla Rohini Atcha Krishnam Raju Kuthati Bhaskar Anren Hu Puchakayala Muralidhar Reddy 《Molecules (Basel, Switzerland)》2021,26(7)
Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles 5a–r were designed and synthesized via the click reaction. The ligands were well characterized using 1H-, 13C-NMR, elemental analysis and ESI-mass spectrometry. The in silico binding propinquities of the ligands were studied sequentially in the active region of VEGFR-2 using the Molegro virtual docker. All the compounds produced remarkable interactions and potentially inhibitory ligands against VEGFR-2 were obtained with high negative binding energies. Drug-likeness was assessed from the ADME properties. Cytotoxicity of the test compounds was measured against HeLa and HUH-7 tumor cells and NIH/3T3 normal cells by MTT assay. Compound 5h showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC50 values of 4.5 and 7.7 μM respectively. Interestingly, the compounds 5a–r did not show any cytotoxicity towards the normal cell lines. The results advance the position of substituted triazoles in the area of drug design with no ambiguity. 相似文献
993.
建立了实时荧光聚合酶链式反应( PCR)偶联高特性核酸侵入反应检测单核苷酸多态性( SNP)的方法。优化了体系中flap核酸内切酶1(FEN1酶)和野生型检测探针等用量,确定了最佳反应条件,即FEN1酶用量为1.5 U,野生型检测探针用量为0.125μmol/L,0.5μmol/L Invader突变型检测探针,各0.25μmol/L通用野生型( VIC)和突变型( FAM)荧光共振转移发卡探针,显著降低了野生型样本和突变型样本背景信号,避免了背景信号对检测结果分型的干扰。采用本方法对编码乙醛脱氢酶2( ALDH2)基因ALDH2*2位点21例样本、细胞色素P4502C19基因CYP2C19*2和CYP2C19*3位点各19例样本进行分型检测,结果表明, AL-DH2*2位点GG纯合10例,GA杂合8例,AA纯合3例;CYP2C19*2位点GG纯合9例,GA杂合8例,AA纯合2例;CYP2C19*3位点GG纯合18例,GA杂合1例。使用焦磷酸测序进行验证,两种方法检测结果一致。本方法特异性好、操作简便、耗时短、成本低,可实现对SNP单管闭管无污染的分型检测。 相似文献
994.
An affinity improved single-chain antibody from phage display of a library derived from monoclonal antibodies detects fumonisins by immunoassay 总被引:1,自引:0,他引:1
Zu-Quan Hu He-Ping Li Ping Wu Ya-Bo Li Zhu-Qing Zhou Jing-Bo Zhang Jin-Long Liu Yu-Cai Liao 《Analytica chimica acta》2015
Fumonisin B analogs, particularly FB1, FB2, and FB3, are major mycotoxins found in cereals. Single-chain fragment variable (scFv) antibodies represent a promising alternative immunoassay system. A phage-displayed antibody library derived from four monoclonal antibodies (mAbs) generated against FB1 was used to screen high binding affinity scFv antibodies; the best candidate was designated H2. Surface plasmon resonance measurements confirmed that the H2 scFv displayed a 82-fold higher binding affinity than its parent mAb. Direct competitive enzyme-linked immunosorbent assay demonstrated that the H2 antibody could competitively bind to free FB1, FB2, and FB3, with an IC50 of 0.11, 0.04, and 0.10 μM, respectively; it had no cross-reactivity to deoxynivalenol, nivalenol and aflatoxin. Validation assays with naturally contaminated samples revealed a linear relationship between the H2 antibody-based assay results and chemical analysis results, that could be expressed as y = 1.7072x + 5.5606 (R2 = 0.8883). Homology modeling of H2 revealed a favorable binding structure highly complementary to the three fumonisins. Molecular docking analyses suggested that the preferential binding of the H2 scFv to FB2 was due to the presence of a hydrogen radical in its R1 position, leading to a proper electrostatic matching and hydrophobic interaction. The H2 scFv antibody can be used for the rapid, accurate, and specific detection of fumonisin contamination in agricultural samples. 相似文献
995.
Focal adhesion kinase (FAK) has been identified as a potential therapeutic target for the treatment of metastatic cancers. Herein we describe the design, synthesis and optimization of a direct activity sensor for FAK and its application to screening FAK inhibitors. We find that the position of the sensing moiety, a phosphorylation-sensitive sulfonamido-oxine fluorophore, can dramatically influence the performance of peptide sensors for FAK. Real-time fluorescence activity assays using an optimized sensor construct, termed FAKtide-S2, are highly reproducible (Z' = 0.91) and are capable of detecting as little as 1 nM recombinant FAK. Utilizing this robust assay format, we define conditions for the screening of FAK inhibitors and demonstrate the utility of this platform using a set of well-characterized small molecule kinase inhibitors. Additionally, we provide the selectivity profile of FAKtide-S2 among a panel of closely related enzymes, identifying conditions for selectively monitoring FAK activity in the presence of off-target enzymes. In the long term, the chemosensor platform described in this work can be used to identify novel FAK inhibitor scaffolds and potentially assess the efficacy of FAK inhibitors in disease models. 相似文献
996.
997.
998.
Hanna Goh Tae Kyu Nam Amanpreet Singh Narinder Singh Doo Ok Jang 《Tetrahedron letters》2017,58(11):1040-1045
We synthetized a sulfonamide-based dipodal receptor capable of recognizing Ag+ selectively in water in the presence of other possible competing cations through color change. The resultant Ag-complex showed suitability as a chemosensor for the sensing of I? ions in water in the presence of other anions through a cation displacement process. The detection limits of the receptor for Ag+ and of the resultant complex for I? were identified as 2.43 and 5.31 μM, respectively. 相似文献
999.
夏兵伟 《中国无机分析化学》2015,5(1)
火法试金最常用的为铅试金,当物料中铋含量>15%时铅试金分析方法测定银量结果精密度差,且结果偏低。本文重点研究了铋试金测定高铋铅阳极泥中的银量方法;铋试金和铅试金方法过程对比;铋试金方法中杂质元素Sb、Cu、As、Ni、Pb的干扰;铋试金过程中铋扣直接溶解滴定和铋扣灰吹二次试金方法对比。通过多家单位对精密度和回收率的考察,认为该方法准确、可靠。 相似文献
1000.
Tracing Binding Modes in Hit‐to‐Lead Optimization: Chameleon‐Like Poses of Aspartic Protease Inhibitors
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Maren Kuhnert Dr. Helene Köster Dr. Ruben Bartholomäus Dr. Ah Young Park Amir Shahim Prof. Dr. Andreas Heine Dr. Holger Steuber Prof. Dr. Gerhard Klebe Prof. Dr. Wibke E. Diederich 《Angewandte Chemie (International ed. in English)》2015,54(9):2849-2853
Successful lead optimization in structure‐based drug discovery depends on the correct deduction and interpretation of the underlying structure–activity relationships (SAR) to facilitate efficient decision‐making on the next candidates to be synthesized. Consequently, the question arises, how frequently a binding mode (re)‐validation is required, to ensure not to be misled by invalid assumptions on the binding geometry. We present an example in which minor chemical modifications within one inhibitor series lead to surprisingly different binding modes. X‐ray structure determination of eight inhibitors derived from one core scaffold resulted in four different binding modes in the aspartic protease endothiapepsin, a well‐established surrogate for e.g. renin and β‐secretase. In addition, we suggest an empirical metrics that might serve as an indicator during lead optimization to qualify compounds as candidates for structural revalidation. 相似文献