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61.
Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of sumatriptan 总被引:1,自引:0,他引:1
The aim of this investigation was to prepare microemulsions containing sumatriptan (ST) and sumatriptan succinate (SS) to
accomplish rapid delivery of drug to the brain in acute attacks of migraine and perform comparative in vivo evaluation in
rats. Sumatriptan microemulsions (SME)/sumatriptan succinate microemulsions (SSME) were prepared using titration method and
characterized for drug content, globule size and size distribution, and zeta potential. Biodistribution of SME, SSME, sumatriptan
solution (SSS), and marketed product (SMP) in the brain and blood of Swiss albino rats following intranasal and intravenous
(IV) administrations were examined using optimized technetium-labeled (99mTc-labeled) ST formulations. The pharmacokinetic parameters, drug targeting efficiency (DTE), and direct drug transport (DTP)
were derived. Gamma scintigraphy imaging of rat brain following IV and intranasal administrations were performed to ascertain
the localization of drug. SME and SSME were transparent and stable with mean globule size 38±20 nm and zeta potential between
−35 to −55 mV. Brain/blood uptake ratios at 0.5 hour following IV administration of SME and intranasal administrations of
SME, SMME, and SSS were found to be 0.20, 0.50, 0.60, and 0.26, respectively, suggesting effective transport of drug following
intranasal administration of microemulsions. Higher DTE and DTP for mucoadhesive microemulsions indicated more effective targeting
following intranasal administration and best brain targeting of ST from mucoadhesive microemulsions. Rat brain scintigraphy
endorsed higher uptake of ST into the brain. Studies conclusively demonstrated rapid and larger extent of transport of microemulsion
of ST compared with microemulsion of SS, SMP, and SSS into the rat brain. Hence, intranasal delivery of ST microemulsion developed
in this investigation can play a promising role in the treatment of acute attacks of migraine.
Published: January 20, 2006 相似文献
62.
The purpose of this investigation was to evaluate the effect of formulation factors on in vitro permeation of moxifloxacin
from aqueous drop through freshly excised goat, sheep, and buffalo corneas. Aqueous isotonic ophthalmic solutions of moxifloxacin
hydrochloride of different concentrations (pH 7.2) or 0.5% (wt/vol) solutions of different pH or 0.5% solutions (pH 7.2) containing
different preservatives were made. Permeation characteristics of drug were evaluated by putting 1 mL formulation on freshly
excised cornea (0.50 cm2) fixed between donor and receptor compartments of an all-glass modified Franz diffusion cell and measuring the drug permeated
in the receptor (containing 10 mL bicarbonate ringer at 37°C under stirring) by spectrophotometry at 291 nm, after 120 minutes.
Statistical analysis was done by one-way analysis of variance (ANOVA) followed by Dunnett’s test. Increase in drug concentration
in the formulation resulted in an increase in the quantity permeated but a decrease in percentage permeation. Increase in
pH of the solution from 5.5 to 7.2 increased drug permeation, indicating pH-dependent transport. Compared with control formulation,
moxifloxacin 0.5% (wt/vol) solution (pH 7.2) containing disodium edetate (EDTA) (0.01% wt/vol) produced significantly (P<.05) higher permeation with all the corneas. Formulation with benzyl alcohol significantly (P<.05) increased permeation with buffalo cornea compared with its control. Presence of benzalkonium chloride (BAK) (0.01% wt/vol)
and EDTA (0.01% wt/vol) in the formulation increased permeation to the maximum with all the corneas. The results suggest that
moxifloxacin 0.5% ophthalmic solution (pH 7.2) containing BAK (0.01%) and EDTA (0.01%) provides increased in vitro ocular
availability through goat, sheep, and buffalo corneas.
Published: February 10, 2006
Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi-110017, India 相似文献
63.
64.
The 2.1-A-resolution crystal structure of the novel mitochondrial and chloroplastic metalloendopeptidase, AtPreP1, revealed a unique peptidasome structure, in which the two halves of the enzyme completely enfold a huge proteolytic cavity. Based on the structure, we proposed a novel mechanism for proteolysis involving hinge-bending motions, which cause the protease to open and close in response to substrate binding. We generated four double-mutants of AtPreP1 by introducing cysteines at positions where disulfide bonds can be formed in order to lock and unlock the protease and tested the activity under oxidizing and reducing conditions. The overall results support the proposed mechanism. 相似文献
65.
We have analysed 385 mitochondrial and 567 chloroplastic signal sequences of proteins found in the organellar proteomes of Arabidopsis thaliana. Despite overall similarities, the first 16 residues of transit peptides differ remarkably. To test the hypothesis that the N-terminally truncated transit peptides would redirect chloroplastic precursor proteins to mitochondria, we studied import of the N-terminal deletion mutants of ELIP, PetC and Lhcb2.1. The results show that the deletion mutants were neither imported into chloroplasts nor miss-targeted to mitochondria in vitro and in vivo, showing that the entire transit peptide is necessary for correct targeting as well as miss-sorting. 相似文献
66.
Predmore BL Kondo K Bhushan S Zlatopolsky MA King AL Aragon JP Grinsfelder DB Condit ME Lefer DJ 《American journal of physiology. Heart and circulatory physiology》2012,302(11):H2410-H2418
Diallyl trisulfide (DATS), a polysulfide constituent found in garlic oil, is capable of the release of hydrogen sulfide (H(2)S). H(2)S is a known cardioprotective agent that protects the heart via antioxidant, antiapoptotic, anti-inflammatory, and mitochondrial actions. Here, we investigated DATS as a stable donor of H(2)S during myocardial ischemia-reperfusion (MI/R) injury in vivo. We investigated endogenous H(2)S levels, infarct size, postischemic left ventricular function, mitochondrial respiration and coupling, endothelial nitric oxide (NO) synthase (eNOS) activation, and nuclear E2-related factor (Nrf2) translocation after DATS treatment. Mice were anesthetized and subjected to a surgical model of MI/R injury with and without DATS treatment (200 μg/kg). Both circulating and myocardial H(2)S levels were determined using chemiluminescent gas chromatography. Infarct size was measured after 45 min of ischemia and 24 h of reperfusion. Troponin I release was measured at 2, 4, and 24 h after reperfusion. Cardiac function was measured at baseline and 72 h after reperfusion by echocardiography. Cardiac mitochondria were isolated after MI/R, and mitochondrial respiration was investigated. NO metabolites, eNOS phosphorylation, and Nrf2 translocation were determined 30 min and 2 h after DATS administration. Myocardial H(2)S levels markedly decreased after I/R injury but were rescued by DATS treatment (P < 0.05). DATS administration significantly reduced infarct size per area at risk and per left ventricular area compared with control (P < 0.001) as well as circulating troponin I levels at 4 and 24 h (P < 0.05). Myocardial contractile function was significantly better in DATS-treated hearts compared with vehicle treatment (P < 0.05) 72 h after reperfusion. DATS reduced mitochondrial respiration in a concentration-dependent manner and significantly improved mitochondrial coupling after reperfusion (P < 0.01). DATS activated eNOS (P < 0.05) and increased NO metabolites (P < 0.05). DATS did not appear to significantly induce the Nrf2 pathway. Taken together, these data suggest that DATS is a donor of H(2)S that can be used as a cardioprotective agent to treat MI/R injury. 相似文献
67.
Jain V Baitharu I Barhwal K Prasad D Singh SB Ilavazhagan G 《Cellular and molecular neurobiology》2012,32(4):599-611
Hypobaric hypoxia (HH) induced neurodegeneration has been attributed to several factors including increased oxidative stress, glutamate excitotoxicity, decreased growth factors, apoptosis, etc. Though enriched environment (EE) has been known to have beneficial effects in various neurological disorders, its effect on HH mediated neurodegeneration remains to be studied. Therefore, the present study was conducted to explore the effect of EE on HH induced neurodegeneration. Male Sprague-Dawley rats were placed in enriched and standard conditions during exposure to HH (7 days) equivalent to an altitude of 25,000 ft. The effect of EE on oxidative stress markers, apoptosis, and corticosterone level in hippocampus was investigated. EE during exposure to HH was found to decrease neurodegeneration as evident from decreased caspase 3 expression and LDH leakage. However, no significant changes were observed in ROS, MDA, and antioxidant status of hippocampus. HH elevates corticosterone level and affected the diurnal corticoid rhythm which may contribute to neurodegeneration, whereas EE ameliorate this effect. Because of the association of neurotrophins and stress and/or corticosterone the BDNF and NGF levels were also examined and it was found that HH decreases their level but concurrent exposure to EE maintains their level. Moreover, inhibition of Tyrosine kinase receptor (Trk) with K252a nullifies the protective effect of EE, whereas Trk activation with agonist, amitriptyline showed protective effect similar to EE. Taken together, we conclude that EE has a potential to ameliorate HH mediated neuronal degeneration which may act through antioxidant independent pathway by modulation of neurotrophins. 相似文献
68.
Ernstrom GG Weimer R Pawar DR Watanabe S Hobson RJ Greenstein D Jorgensen EM 《Genetics》2012,191(2):461-475
The vacuolar-type ATPase (V-ATPase) is a proton pump composed of two sectors, the cytoplasmic V(1) sector that catalyzes ATP hydrolysis and the transmembrane V(o) sector responsible for proton translocation. The transmembrane V(o) complex directs the complex to different membranes, but also has been proposed to have roles independent of the V(1) sector. However, the roles of the V(1) sector have not been well characterized. In the nematode Caenorhabditis elegans there are two V(1) B-subunit genes; one of them, vha-12, is on the X chromosome, whereas spe-5 is on an autosome. vha-12 is broadly expressed in adults, and homozygotes for a weak allele in vha-12 are viable but are uncoordinated due to decreased neurotransmission. Analysis of a null mutation demonstrates that vha-12 is not required for oogenesis or spermatogenesis in the adult germ line, but it is required maternally for early embryonic development. Zygotic expression begins during embryonic morphogenesis, and homozygous null mutants arrest at the twofold stage. These mutant embryos exhibit a defect in the clearance of apoptotic cell corpses in vha-12 null mutants. These observations indicate that the V(1) sector, in addition to the V(o) sector, is required in exocytic and endocytic pathways. 相似文献
69.
Gnanesh AU Krishna V Kumar RS Venkatesh Kumar SR Shashidhar HE 《Indian journal of experimental biology》2012,50(2):164-170
The Malnad region located in the Western Ghats of Karnataka is known for the cultivation of indigenous rain fed land race cultivar of rice. The present study was to investigate the callogenic and caulogenic potentialities of the two indigenous rice cultivar namely Karimundaga and Kanadatumba using dehusked mature embryo explants. For callus and shoot bud differentiation, the explants were cultured on Murashige and Skoog (MS) medium supplemented with 2,4-D (1-3 mg/L), IAA (1-2 mg/L), Kn (1-4 mg/L) and BAP (1-4 mg/L). The morphogenic potentialities of the two rice cultivar differed in texture of callus. In both the cultivar callogenic frequency was optimized at 1 mg/L 2,4-D concentration, it was 94% in Karimundaga and 58% in Kanadatumba. Supplementation of IAA either alone (1-2 mg/L) or in combination with Kn or BAP at 1 to 4 mg/L concentration of each induces shoot bud differentiation from the calli. In the cultivar Karimundaga caulogenic frequency was highest (10.60 +/- 2.55) at 1.0 mg/L IAA and 4.0 mg/L BAP concentration. While in the cultivar Kanadatumba highest number of shoot buds (7.90 +/- 2.69) was differentiated at 1.0 mg/L IAA and 4.0 mg/L Kn concentration. The calli derived regenerants were successfully acclimatized in the greenhouse and agro-morphological variations were evaluated. The growth characteristics and yield related parameters exhibited by in vitro plants were lower than the in vivo plants. 相似文献
70.