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991.
Genistein is an isoflavone and phytoestrogen that is a potent inhibitor of cell proliferation and angiogenesis. This study was designed to investigate the binding of genistein to human serum albumin (HSA) under physiological conditions with drug concentrations in the range of 6.7 × 10−6 to 2.0 × 10−5 mol L−1 and HSA concentration at 1.5 × 10−6 mol L−1. Fluorescence quenching methods in combination with Fourier transform infrared (FT-IR) spectroscopy and circular dichroism (CD) spectroscopy was used to determine the binding mode, the binding constant and the protein structure changes in the presence of genistein in aqueous solution. Changes in the CD spectra and FT-IR spectra were observed upon ligand binding, and the degree of tryptophan fluorescence quenching change did significantly in the complexes. These data have proved the change in protein secondary structure accompanying ligand binding. The change in tryptophan fluorescence intensity was used to determine the binding constants. The thermodynamic parameters, the enthalpy change (ΔH) and the entropy change (ΔS) were calculated to be −22.24 kJ mol−1and 19.60 J mol−1 K−1 according to the van’t Hoff equation, which indicated that hydrophobic and electrostatic interactions play the main role in the binding of genistein to HSA. 相似文献
992.
993.
Stearns BA Anker N Arruda JM Campbell BT Chen C Cramer M Hu T Jiang X Park K Ren KK Sablad M Santini A Schaffhauser H Urban MO Munoz B 《Bioorganic & medicinal chemistry letters》2004,14(5):1295-1298
A novel class of 6-aryl-6H-pyrrolo[3,4-d]pyridazine ligands for the alpha2delta subunit of voltage-gated calcium channels has been described. Substitutions in the aryl ring of the molecule were generally not tolerated, and resulted in diminished binding to the alpha2delta subunit. Modifications to the pyridazine ring revealed numerous permissive substitutions, and detailed SAR studies were carried out in this portion of the molecule. Replacement of the pyridazine ring methyl group with an aminomethyl functionality provided greatly improved potency over the initial lead. The initial lead compound displayed good rat pharmacokinetic properties, and was shown to be efficacious in the Chung model for neuropathic pain in rats. 相似文献
994.
A new class of methionine aminopeptidase (MetAP) inhibitors, which contain an internal hydroxamate (N-acyl-N-alkylhydroxylamine) core as the metal-chelating group, has been designed, synthesized, and tested. The compounds exhibited reversible, competitive inhibition against Escherichia coli MetAP as well as human MetAP-1 and MetAP-2. The most potent inhibitor had a K(i) value of 2.5 microM and >20-fold selectivity toward E. coli MAP. 相似文献
995.
Bürli RW McMinn D Kaizerman JA Hu W Ge Y Pack Q Jiang V Gross M Garcia M Tanaka R Moser HE 《Bioorganic & medicinal chemistry letters》2004,14(5):1253-1257
Novel DNA minor-groove binding ligands with a promising antibacterial profile are described. Apart from excellent in vitro potency against multiple Gram-positive bacterial strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), and penicillin-intermediate Streptococcus pneumoniae (PISP), a small subset of compounds was active against Gram-negative bacteria such as Escherichia coli (E. coli). 相似文献
996.
Yao S Sgarbi PW Marby KA Rabuka D O'Hare SM Cheng ML Bairi M Hu C Hwang SB Hwang CK Ichikawa Y Sears P Sucheck SJ 《Bioorganic & medicinal chemistry letters》2004,14(14):3733-3738
Glyco-optimization (OPopS) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b,g,i,l, and 8u with 2"-amino, 2",3"-diamino, 2",4"-diamino, 3",4"-diamino, 3"-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(-) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1-2 microg/mL range. 相似文献
997.
Fifteen compounds of 10-substituted benzylidene anthrone were prepared with moderate yield by reaction of anthrone and substituted benzaldehydes under the presence of pyridine and piperidine as catalyst. Their antitumor activities in vitro were evaluated. The results show that the electron-withdrawing substitutes decrease the activities, the electron-donor substitutes increase the activities; the compound with substitute at ortho or para position has stronger activities than that of compound with the same substitute but located at the meta position. There are six compounds which appear as strong effective inhibition for A-549 cancer cell growth. This is a kind of good leading compound which is worth researching further. 相似文献
998.
999.
1000.
Using intracellular recording in vivo, the bursting behaviors were investigated in the neurons of chronically compressed dorsal root ganglia of the adult rat. In most cases, the first spike of a burst emerged from amplitude-increasing damped subthreshold membrane potential oscillation (SMPO) and the discharge terminated by an amplitude-decreasing damped SMPO. The rhythms of these bursting behaviors are all irregular. Since some researchers found that the stochastic dynamics can also produce similar bursting pattern, the deterministic dynamics of interevent interval (IEI) series obtained from raw membrane potential recording was detected by extraction of the hierarchy of unstable periodic orbits (UPOs) in the windowed IEI series. The results showed a number of statistically significant UPOs of order-one, order-two, and order-three. These orbits form a complex but predictable lattice of regions in which the dynamics of the bursting occurrence is deterministic. Based on a complete classification scheme, the investigated bursting can be depicted by the elliptic bursting dynamics. The significance of the finding that a neuron in the injured dorsal root ganglion has such dynamics is also discussed. 相似文献