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61.
K Salat T Librowski A Moniczewski K Stanisz-Wallis K Wieckowski B Malawska 《Behavioural pharmacology》2012,23(4):407-416
In this paper, the analgesic, antioedematous, motor-impairing and antioxidant properties of four γ-butyrolactone derivatives (BM113, BM113A, BM138 and BM138A) are described. Pain was induced by thermal (hot-plate test), chemical (writhing test) or mechanical (Randall-Selitto model) stimulation. All in-vivo assays were carried out in mice pretreated intraperitoneally with the test compounds, except for the evaluation of anti-inflammatory and analgesic activities in the carrageenan-induced paw oedema model, in which rats were pretreated orally with these compounds. In the hot-plate assay, BM113A and BM138A dose dependently prolonged the latency of the nociceptive reaction. Their analgesic activity, measured as a median effective dose (ED(50)=4.7 mg/kg), was similar to that of morphine (2.4 mg/kg). In the writhing test, all four compounds, in particular BM113A and BM138A, showed higher potency than the reference drug acetylsalicylic acid (the ED(50) values were 3.7, 2.3 and 46.1 mg/kg, respectively). BM138 caused a dose-dependent diminution of paw oedema (up to 49%) in the carrageenan model and BM138A at 200 mg/kg reduced mechanical hyperalgesia in the Randall-Selitto test (~30% when compared with the control). None of the γ-butyrolactone derivatives tested at the ED(50) obtained in the hot-plate test influenced the locomotor activity of mice, although in the rotarod test at 24 rpm, BM113A and BM138 at 100 mg/kg showed some motor-impairing properties. In vitro, a concentration-dependent ABTS radical cation-scavenging activity of BM138 and BM138A (up to 80% inhibition of the radical absorbance) was observed. The results of the present study suggest that BM138 and BM138A could be of interest for future investigations as antinociceptive and antioedematous agents with potential free radical-scavenging properties. 相似文献
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Kinga K. Borowicz Jarogniew J. Łuszczki Stanisław J. Czuczwar 《Pharmacological reports : PR》2009,61(4):621-630
2-Methyl-6-phenylethynyl-pyridine (MPEP), a selective noncompetitive mGluR5 antagonist, influences the action of conventional antiepileptic drugs in amygdala-kindled seizures in rats. MPEP alone (up to 40 mg/kg) did not affect any seizure parameter. Moreover, the common treatment of MPEP with either carbamazepine or phenytoin (administered at subeffective doses) did not result in any anticonvulsant action in kindled rats. However, when combined with subprotective doses of valproate or phenobarbital, MPEP significantly shortened seizure and afterdischarge durations. Importantly, combinations of MPEP with the two antiepileptics did not have the adverse effects of impaired motor performance or long-term memory in rats. Our data indicate that MPEPmay positively interact with some conventional antiepileptic drugs in the amygdala-kindling model of complex partial seizures. 相似文献
65.
Borowicz KK Banach M Zarczuk R Lukasik D Luszczki JJ Czuczwar SJ 《Psychopharmacology》2007,195(2):167-174
Rationale Epilepsy often coexists with depression. Therefore, the probability of simultaneous treatment with antiepileptics and antidepressants
and the possibility of interactions between them are relatively high.
Objective The effects of acute and chronic administration of mianserin on the protective activity of valproate (VPA), carbamazepine,
phenytoin, and phenobarbital were evaluated in the maximal electroshock in mice.
Materials and methods Animals were subjected to electroconvulsions. Undesired effects were evaluated in the chimney test (motor impairment) and
passive-avoidance task (memory deficit). Brain concentrations of antiepileptic drugs were assessed by immunofluorescence.
Results When given acutely, mianserin (at doses greater than or equal to 20 mg/kg) significantly raised the electroconvulsive threshold.
The antidepressant, at the subanticonvulsant doses, enhanced the anticonvulsant action of carbamazepine, phenytoin, and VPA.
Mianserin administered chronically at 30 mg/kg significantly decreased the electroconvulsive threshold. In contrast to acute
treatment, the antidepressant at subeffective doses diminished the anticonvulsant activity of VPA and phenytoin. Mianserin
given either acutely or chronically did not affect the brain concentrations of antiepileptic drugs, so a pharmacokinetic contribution
to the observed interactions is not probable.
Acute and chronic treatment with mianserin and its combinations with antiepileptic drugs did not impair either motor coordination
or long-term memory.
Conclusion Although acute application of mianserin may potentiate the anticonvulsant action of some antiepileptics, its chronic administration
can lead to the opposite effect. Therefore, as far as the presented results can be transferred to clinical conditions, the
antidepressant therapy with mianserin should be limited or even avoided in epileptic patients. 相似文献
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Kinga Lis Grazyna Odrowaz-Sypniewska Wies?aw Nowacki 《Chirurgia narzadów ruchu i ortopedia polska》2005,70(6):407-410
Osteoarthritis is the greatest problem of aging population. It concerns particularly women over 65 years of age, in considerable degree limiting their locomotion activity. In recent years many different opinions on pathogenesis of osteoarthritis were presented, among them on the role of some growth factors like IGF-1 and TGF-beta playing an anabolic role in cartilage metabolism. The aim of our study was to compare the concentration of IGF-1 in clinically healthy women and women with coxarthrosis and to evaluate the association between IGF-1 in the serum and synovial fluid in relation to disease etiology. We found that in coxarthrosis of either idiopathic, necrotic or dysplastic etiology serum IGF-1 level was significantly lower than in control women (84.4; 76.1; 86.7 vs. 147.7 microg/ml). Concentration of IGF-1 in different groups of patients was similar or lower in synovial fluid than in the serum. Consistently decreased IGF-1 was found in synovial fluid (42.3 microg/ml) of patients with coxarthosis of necrotic origin. Our results suggest that low IGF-1 values, especially in synovial fluid, are in association with type of osteoarthritic changes within the joint, independently on age. 相似文献
68.
INTRODUCTION: Nowadays, doctors strongly recommend physical activity for asthmatic children, since the resulting improved physical fitness and psychological change also raise the quality of life. AIMS: The aim of this study was to compare the physical fitness of asthmatic children who regularly participate in therapeutic swimming, with asthmatic children who do not participate in this training and with non-swimming, healthy children using the 12 minute free running, Cooper test. METHOD: The children from the swimmer asthmatic group (n= 51, age = 9-22 yrs) took part in a special, long term, swimming exercise program (Gyene method). Whereas, the non-swimmer asthmatics (n = 28, age = 8-22 yrs) and the healthy children (n: 179, age: 9-22 yrs) only took part in the normal school physical education classes. Fitness was measured using the Cooper test. RESULTS: Data was collected from 258 subjects and showed that the fitness of swimmer asthmatics is significantly better than that of the non-swimmer asthmatics and even better than that of the healthy subjects (swimmer/ non swimmer asthmatic p = 0.01; swimmer asthmatic/ healthy p < 0.0001 Chi(2) test). The difference in the fitness acquired from swimming was the most pronounced for the 8-11 years old asthmatics, presumably because of greater motivational factors. No differences were found between genders for the two asthmatic groups, whereas healthy boys were found to have significantly greater levels of fitness than healthy girls. CONCLUSIONS: Fitness is substantially increased with regular swimming. The favourable effects of swimming are expressed not only in comparison with the non-swimmer asthmatics but with the healthy subjects too. The regular therapeutic swimming program helps the formation of running fitness too. 相似文献
69.
Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases 总被引:7,自引:0,他引:7
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Sieprawska-Lupa M Mydel P Krawczyk K Wójcik K Puklo M Lupa B Suder P Silberring J Reed M Pohl J Shafer W McAleese F Foster T Travis J Potempa J 《Antimicrobial agents and chemotherapy》2004,48(12):4673-4679
Cathelicidin LL-37 is one of the few human bactericidal peptides with potent antistaphylococcal activity. In this study we examined the susceptibility of LL-37 to proteolytic degradation by two major proteinases produced by Staphylococcus aureus, a metalloproteinase (aureolysin) and a glutamylendopeptidase (V8 protease). We found that aureolysin cleaved and inactivated LL-37 in a time- and concentration-dependent manner. Analysis of the generated fragments by mass spectroscopy revealed that the initial cleavage of LL-37 by aureolysin occurred between the Arg19-Ile20, Arg23-Ile24, and Leu31-Val32 peptide bonds, instantly annihilating the antibacterial activity of LL-37. In contrast, the V8 proteinase hydrolyzed efficiently only the Glu16-Phe17 peptide bond, rendering the C-terminal fragment refractory to further degradation. This fragment (termed LL-17-37) displayed antibacterial activity against S. aureus at a molar level similar to that of the full-length LL-37 peptide, indicating that the antibacterial activity of LL-37 resides in the C-terminal region. In keeping with LL-37 degradation by aureolysin, S. aureus strains that produce significant amounts of this metalloprotease were found to be less susceptible to LL-17-37 than strains expressing no aureolysin activity. Taken together, these data suggest that aureolysin production by S. aureus contributes to the resistance of this pathogen to the innate immune system of humans mediated by LL-37. 相似文献
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