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991.
Treatment of trans-[IrCl(CO)(PPh3)2] with Ph2PCH2CH2NH2 in refluxing para-xylene gave (OC-6-43)-[Ir(H)(Cl)(Ph2PCH2CH2NH2)2]Cl (1) which interacted with K[BH(s-Bu3)] to produce a mixture of (OC-6-22)-[IrH2(Ph2PCH2CH2NH2)2]Cl (2a) and (OC-6-32)-[Ir(H)(Cl)(Ph2PCH2CH2NH2)2]Cl (2b). The trans-dihydride 2a was isolated in pure form from the reaction between 1 and KOH/i-PrOH. Different from its isoelectronic (P,N)2-coordinated RuII analogues, the cationic chloro hydrido complex 1 does not act as a catalyst for the direct hydrogenation of acetophenone by molecular H2, if activated by strong alkoxide base, but rather catalyzes the transfer hydrogenation of the CO bond with methanol or isopropanol as proton/hydride sources. Dihydrido complex 2a is ascribed the role of the actual catalyst as it supports the transfer hydrogenation reaction even in the absence of base. The crystal structure of the addition compound 1 · 2EtOH has been determined. 相似文献
992.
Masahiko Maekawa Toshie Minematsu Kunihisa Sugimoto Yusaku Suenaga 《Inorganica chimica acta》2004,357(12):3456-3472
New five mono- and dinuclear Ir hydrido complexes with polydentate nitrogen ligands, [Ir(H)2(PPh3)2(tptz)]PF6 (1), [Ir2(H)4(PPh3)4(tptz)](PF6)2 · 2H2O (2 · 2H2O), [Ir(H)2(PPh3)2(tppz)]BF4 (3), [Ir2(H)4(PPh3)4(tppz)](BF4)2 (4) and [Ir2(H)4(PPh3)4(bted)](BF4)2 · 6CHCl3 (5 · 6CHCl3), were systematically prepared by the reactions of the precursor Ir hydrido complex [Ir(H)2(PPh3)2(Me2CO)2]X (X=PF6 and BF4) with 2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz), 2,3,5,6-tetrakis(2-pyridyl)pyrazine (tppz) and 1,4-bis(2,2′:6′,2″-terpyridine-4′-yl)benzene (bted), and their structures and properties were characterized in the solid state and in solution. Each of the Ir hydrido complexes with polydentate nitrogen ligands crystallographically described a unique coordination mode. Their 1H NMR spectra demonstrated unusual 1H NMR chemical shifts of pyridyl rings that are likely induced by the ring current effect of neighboring ligands. 相似文献
993.
Swarup Chattopadhyay 《Inorganica chimica acta》2004,357(3):764-768
2-Hydroxypyridine (Hhp), 2-hydroxynicotinic acid (HnicOH) and 6-hydroxypicolinic acid (HpicOH) react with Re2Cl4(μ-dppm)2 (dppm=Ph2PCH2PPh2) to afford the complexes Re2(η2-hp)Cl3(μ-dppm)2 (1), Re2(η2-HnicO)Cl3(μ-dppm)2 (2) and Re2(μ-picO)2(μ-dppm)2 (3). The identities of 1 and 2 have been established by single-crystal X-ray structure determinations (Re-Re distances of 2.2602(3) and 2.2539(3) Å, respectively) and they are shown to have unsymmetrical structures with staggered rotational geometries and trans, cis coordination of the pair of μ-dppm ligands. The crystal of 2 that was used in the structure determination was found to be of composition 2Re2(η2-HnicO)Cl3(μ-dppm)2 · Re2Cl6(μ-dppm)2 · 2.906CH2Cl2. The structure of Re2Cl6(μ-dppm)2 in this crystal is compared with structures reported in the literature for other crystals that contain this edge-sharing bioctahedral dirhenium(III) complex. 相似文献
994.
Copper(II) complexes of a series of linear pentadentate ligands containing two benzimidazoles, two thioether sulfurs and a amine nitrogen, viz. N,N′-bis{4′-(2″-benzimidazolyl)(methyl)-3′-thiabutyl}amine(L1), N,N′-bis{4′-(2″-benzimidazolyl)(methyl)-3′-thiabutyl}N-methylamine (L2), 2,6-bis{4′-(2″-benzimidazolyl)(methyl)-3′-thiabutyl}pyridine(L3), N,N′-bis{4′-(2″-benzimidazolyl)-2′-thiabutyl}amine (L4), N,N′-bis{4′-(2″-benzimidazolyl)-2′-thiabutyl}N-methylamine (L5) and 2,6-bis{4′-(2″-benzimidazolyl)-2′-thiabutyl}-3pyridine (L6) have been isolated and characterized by electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes, [Cu(L1)](BF4)2 (1) and [Cu(L2)](BF4)2 (4) have been structurally characterized by X-ray crystallography. The coordination geometries around copper(II) in 1 and 4 are described as trigonal bipyramidal distorted square based pyramidal geometry (TBDSBP). The distorted CuN3S basal plane in them is comprised of amine nitrogen, one thioether sulphur and two benzimidazole nitrogens and the other thioether sulfur is axially coordinated. The ligand field spectra of all the complexes are consistent with a mostly square-based geometry in solution. The EPR spectra of complexes [Cu(L1)](BF4)2 (1), [Cu(L1)](NO3)2 (2), [Cu(L2)](BF4)2 (4) and [Cu(L3)](ClO4)2 (6) are consistent with two species indicating the dissociation/disproportionation of the complex species in solution. All the complexes exhibit an intense CT band in the range 305-395 nm and show a quasireversible to irreversible CuII/CuI redox process with relatively positive E1/2 values, which are consistent with the presence of two-coordinated thioether groups. The addition of N-methylimidazole (mim) replaces the coordinated thioether ligands in solution, as revealed from the negative shift (222-403 mV) in the CuII/CuI redox potential. The present study reveals that the effect of incorporating an amine nitrogen donor into CuN2S2 complexes is to generate an axial copper(II)-thioether coordination and also to enforce lesser trigonality on the copper(II) coordination geometry. 相似文献
995.
Sahin U Weskamp G Kelly K Zhou HM Higashiyama S Peschon J Hartmann D Saftig P Blobel CP 《The Journal of cell biology》2004,164(5):769-779
All ligands of the epidermal growth factor receptor (EGFR), which has important roles in development and disease, are released from the membrane by proteases. In several instances, ectodomain release is critical for activation of EGFR ligands, highlighting the importance of identifying EGFR ligand sheddases. Here, we uncovered the sheddases for six EGFR ligands using mouse embryonic cells lacking candidate-releasing enzymes (a disintegrin and metalloprotease [ADAM] 9, 10, 12, 15, 17, and 19). ADAM10 emerged as the main sheddase of EGF and betacellulin, and ADAM17 as the major convertase of epiregulin, transforming growth factor alpha, amphiregulin, and heparin-binding EGF-like growth factor in these cells. Analysis of adam9/12/15/17-/- knockout mice corroborated the essential role of adam17-/- in activating the EGFR in vivo. This comprehensive evaluation of EGFR ligand shedding in a defined experimental system demonstrates that ADAMs have critical roles in releasing all EGFR ligands tested here. Identification of EGFR ligand sheddases is a crucial step toward understanding the mechanism underlying ectodomain release, and has implications for designing novel inhibitors of EGFR-dependent tumors. 相似文献
996.
Brenk R Meyer EA Reuter K Stubbs MT Garcia GA Diederich F Klebe G 《Journal of molecular biology》2004,338(1):55-75
The enzyme tRNA-guanine transglycosylase (TGT) is involved in the pathogenicity of Shigellae. As the crystal structure of this protein is known, it is a putative target for the structure-based design of inhibitors. Here we report a crystallographic study of several new ligands exhibiting a 2,6-diamino-3H-quinazolin-4-one scaffold, which has been shown recently to be a promising template for TGT-inhibitors. Crystal structure analysis of these complexes has revealed an unexpected movement of the side-chain of Asp102. A detailed analysis of the water network disrupted by this rotation has lead to the derivation of a new composite pharmacophore. A virtual screening has been performed based on this pharmacophore hypothesis and several new inhibitors of micromolar binding affinity with new skeletons have been discovered. 相似文献
997.
In the present study, novel 2-cyclopropyl-3-ethynyl-4-(4-fluorophenyl) quinolines (4a-l) were recognized and evaluated as G-Protein Coupled Receptor (GPCR) ligands through molecular evaluations. Thrombin mediates adhesion of mast cell, a type of cell abundantly found in connective tissue and releasing histamine and other substances during inflammatory and allergic reactions, through phosphoinositol 3-kinase pathway. With this background, as preliminary, 4a-l are resolute to be potential leads, designated from their effective phosphoinositol 3-kinase (PI3-Kinase) inhibition potentials, best-docked scores, comparative ligand efficiency, and significant structural attributes evaluated by ab initio simulations. Since thrombin is one of the main reason for various cancer invasion in association with PI3Kinase, a thrombolytic potential of the compounds also analyzed. The experimental in vitro studies confirmed the significant enhancement as PI3Kinase inhibitors and appreciable enhancement in MTT assay of breast and skin cancer cell lines. Significantly, acetophenone substituent in the quinoline scaffold could be coherent to note the significant binding affinity to all the evaluated drug targets. 相似文献
998.
Héctor Torres-Gómez Constantin Daniliuc Dirk Schepmann Bernhard Wünsch 《Bioorganic & medicinal chemistry》2018,26(8):1705-1712
In order to obtain rigid σ1 receptor ligands with defined orientation of pharmacophoric elements, the azapropellane scaffold was chosen. Schmidt rearrangement of propellan-8-ones 6 and 10 provided 3-azapropellan-4-ones 7 and 11. Benzylation of the secondary lactams 7 and 11 followed by LiAlH4 reduction furnished the azapropellanes 4a and 4c, respectively. A second hydrophobic element was introduced by transformation of the alcohols 4a into carbamates 4b. The σ1 affinity of the azapropellanes 4 is strongly dependent on the stereochemistry and the substitution pattern in 12-position. anti-configured azapropellanes anti-4a and anti-4b show higher σ1 affinity than their syn-configured counterparts syn-4a and syn-4b. Conversion of the alcohol anti-4a into the carbamate anti-4b led to increased σ1 affinity, but complete removal of the 12-substituent resulted in the highest σ1 affinity (Ki(4c)?=?17?nM). It can be concluded that the propellane scaffold alone is able to form strong lipophilic interactions and stabilize the ligand–σ1 receptor complex as does usually the primary hydrophobic region. 相似文献
999.
1000.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is associated with various clinico-pathological characteristics such as genetic mutations and viral infections. Therefore, numerous laboratories look out for identifying always new putative markers for the improvement of HCC diagnosis/prognosis. Many molecular profiling studies investigated gene expression changes related to HCC. HepG2 represents a pure cell line of human liver carcinoma, often used as HCC model due to the absence of viral infection. In this study we compare gene expression profiles associated with HepG2 (as HCC model) and normal hepatocyte cells by microarray technology. Hierarchical cluster analysis of genes evidenced that 2646 genes significantly down-regulated in HepG2 cells compared to hepatocytes whereas a further 3586 genes significantly up-regulated. By using the Ingenuity Pathway Analysis (IPA) program, we have classified the genes that were differently expressed and studied the functional networks correlating these genes in the complete human interactome. Moreover, to confirm the differentially expressed genes as well as the reliability of our microarray data, we performed a quantitative Real time RT-PCR analysis on 9 up-regulated and 11 down-regulated genes, respectively. In conclusion this work i) provides a gene signature of human hepatoma cells showing genes that change their expression as a consequence of liver cancer in the absence of any genetic mutations or viral infection, ii) evidences new differently expressed genes found in our signature compared to previous published studies and iii) suggests some genes on which to focus future studies to understand if they can be used to improve the HCC prognosis/diagnosis. 相似文献