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201.
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Sensitization to radiation from an implanted 125I source by sustained intratumoral release of chemotherapeutic drugs 总被引:3,自引:0,他引:3
We have investigated tumor response to low-dose-rate irradiation from an implanted 125I source alone or in conjunction with intratumoral drug administration. The drug (cis-DDP or 5-FU) was incorporated homogeneously into the co-polymer CPP-SA, 20:80, and the polymer/drug rods were implanted in the RIF-1 fibrosarcomas growing subcutaneously in C3H mice. Twenty-four hours later, the tumor was implanted with an 125I seed. Tumor growth time was the end point in these experiments. For implanted 125I sources of different dose rates and implant times giving a range of total doses, a consistent dose-response relationship was shown between tumor growth time and total dose. In other experiments, 125I sources of different specific activities were implanted for periods of time adjusted so that the total dose to the tumor was always the same. When the 125I implant was combined with 5-FU, greater than additive responses were seen for both short (30 h) and long (96 h) 125I treatment times. In contrast, a short-duration (30 h) 125I implant combined with cis-DDP was the least effective treatment, giving a combined response that was no better than additive, whereas 96 h exposure to 125I combined with cis-DDP was the most effective combined treatment. It is conjectured that this inverse dose-rate effect seen when cis-DDP is combined with low-dose rate radiation is related to a cell cycle effect and/or to inhibition of repair of radiation damage by cis-DDP. 相似文献
204.
Methionine sulfoxide reductases protect Ffh from oxidative damages in Escherichia coli 总被引:1,自引:0,他引:1
In proteins, methionine residues are primary targets for oxidation. Methionine oxidation is reversed by methionine sulfoxide reductases A and B, a class of highly conserved enzymes. Ffh protein, a component of the ubiquitous signal recognition particle, contains a methionine-rich domain, interacting with a small 4.5S RNA. In vitro analyses reported here show that: (i) oxidized Ffh is unable to bind 4.5S RNA, (ii) oxidized Ffh contains methionine sulfoxide residues, (iii) oxidized Ffh is a substrate for MsrA and MsrB enzymes; and (iv) MsrA/B repairing activities allow oxidized Ffh to recover 4.5S RNA-binding abilities. In vivo analyses reveal that: (i) Ffh synthesized in the msrA msrB mutant contains methionine sulfoxide residues and is unstable, (ii) msrA msrB mutant requires high levels of Ffh synthesis for growth and (iii) msrA msrB mutation leads to defects in Ffh-dependent targeting of MalF. We conclude that MsrA and MsrB are required to repair Ffh oxidized by reactive oxygen species produced by aerobic metabolism, establishing an as-yet undescribed link between protein targeting and oxidation. 相似文献
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Bekhit AA El-Sayed OA Aboul-Enein HY Siddiqui YM Al-Ahdal MN 《Journal of enzyme inhibition and medicinal chemistry》2004,19(1):33-38
Synthesis of a novel series of structurally related pyrazoloquinoline nucleosides is described. All the newly synthesized compounds were examined for their in vitro antiviral activity against herpes simplex type-1 as shown by two different bioassays, namely; crystal violet staining or the MTS tetrazolium dye measurement. The acute toxicity (LD50) values of the biologically active compounds were determined. 相似文献
208.
Chohan ZH Pervez H Khan KM Rauf A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2004,19(1):51-56
A method is described for the preparation of novel cephalexin-derived furanyl-, thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-containing compounds showing potent antibacterial activity. The binding of these newly synthesized antibacterial agents with metal ions such as cobalt(II), copper(II), nickel(II) and zinc(II) has been studied and their inhibitory properties against various bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae are also reported. These results suggest that metal ions to possess an important role in the designing of metal-based antibacterials and that such complexes are more effective against infectious diseases compared to the uncomplexed drugs. 相似文献
209.
Mamdouh M. Ghorab Heba M. Abdel-Salam Marwa A. El-Sayad Mohammed M. Mekhel 《AAPS PharmSciTech》2004,5(4):63-68
The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried
or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The
tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated
for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to
thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution
studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced
2-way crossover study. Phase-solubility studies indicated an AL-type diagram with inclusion complex of 1∶1 molar ratio. The powder blends and granules of all formulations showed satisfactory
flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation
showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD
in the formulations up to 30%. The mean pharmacokinetic parameters (Cmax, Ke, and area under the curve [AUC]0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam
tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between
tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving
the oral bioavailablity of meloxicam. 相似文献
210.
The purpose of this research was to evaluate beta-cyclodextrin (beta-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of beta-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of beta-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an A(L)-type diagram with inclusion complex of 1:1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formulations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of beta-CD in the formulations up to 30%. The mean pharmacokinetic parameters (C(max), K(e), and area under the curve [AUC](0-infinity)) were significantly increased in presence of beta-CD. These results suggest that beta-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, beta-CD is particularly useful for improving the oral bioavailablity of meloxicam. 相似文献