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排序方式: 共有640条查询结果,搜索用时 15 毫秒
51.
Wolf C Brüss M Hänisch B Göthert M von Kügelgen I Molderings GJ 《Molecular pharmacology》2007,71(1):276-283
The aim of the present study was to challenge potential mechanisms of action underlying the inhibition of tumor cell proliferation by agmatine. Agmatine inhibited proliferation of the human hepatoma cells HepG2, the human adenocarcinoma cells HT29, the rat hepatoma cells McRH7777, and the rat pheochromocytoma cells PC-12. Inhibition of proliferation of HepG2 cells was associated with an abolition of expression of ornithine decarboxylase (ODC) protein and a doubling of mRNA content encoding ODC. In HepG2 cells, silencing of ODC-antizyme-1, but not of antizyme inhibitor, by RNA interference resulted in an increase of agmatine's antiproliferative effect. Thus, the distinct decrease in intracellular polyamine content by agmatine was due to a reduced translation of the synthesizing protein ODC but was not essentially mediated by induction of ODC-antizyme or blockade of antizyme inhibitor. In interaction experiments 1 mM L-arginine, 1 mM D-arginine, 1 mM citrulline, 100 microM N(omega)-nitro-L-arginine methyl ester, 1 and 10 microM sodium nitroprusside, and 1 microM N1-guanyl-1,7-diaminoheptane failed to alter agmatine's antiproliferative effect. Hence, the antiproliferative effect of agmatine in HT29 and HepG2 cells is due to an interaction with neither the NO synthases, the hypusination of eIF5A, nor an agmatine-induced reduction in availability of intracellular L-arginine. L-Arginine and citrulline, but not d-arginine, inhibited tumor cell proliferation by themselves. Their inhibitory effect was abolished after silencing of arginine decarboxylase (ADC) expression by RNA interference indicating the conversion to agmatine by ADC. Finally, in the four cell lines under study, agmatine-induced inhibition of cell proliferation was paralleled by an increase in intracellular caspase-3 activity, indicating a promotion of apoptosis. 相似文献
52.
We measured red blood cell iron incorporation (RBC-inc) in 13 human milk-fed premature infants (birthweight 1037 +/- 289 g, gestational age 27 +/- 2 wk, weight at start of study 1571 +/- 426 g) who were receiving full tube-feedings of human milk fortified with a commercial human milk fortifier (FortHM). The relative RBC-inc of supplemental iron (2 mg/kg/d of ferrous sulfate) was assessed using 57Fe sulfate mixed directly into a 24-h volume of FortHM, and 54Fe sulfate given as a bolus between two FortHM feedings the next day. RBC-inc was similar between the two methods of supplemental iron administration (4.7 +/- 2.5% vs 4.6 +/- 1.5%, respectively). Although these values are lower than RBC-inc expected from iron native to human milk, the relatively large amount of iron in the supplements contributed most of the iron incorporated into RBC by the infants. There was a significant positive correlation between the reticulocyte count and RBC-inc. As the high nutrient (especially calcium) content of the FortHM did not interfere with iron utilization, adding iron directly to FortHM, or incorporating it into commercial fortifiers, may be a practical method to provide iron to premature infants. 相似文献
53.
OBJECTIVE: The purpose of this study was to assess the clinical and economic impact of the introduction of inhaled corticosteroid therapy for asthma in a cohort of children 12 years and younger who were North Carolina Medicaid enrollees.
METHODS: The North Carolina Medicaid claims database was used to retrieve clinical and economic variables for the purpose of this study. The case group, which was comprised of 84 children who started corticosteroid inhaler therapy between March 1994 and March 1995, was followed up for 1 year before and 1 year after the start of the therapy. The control group was comprised of 72 children with similar severity of asthma who remained on any other therapy other than corticosteroids for a continuous 2-year period. Paired t-tests were used to compare differences, and multiple regression analysis was used to adjust for potential confounders.
RESULTS: There was a 58% reduction in hospital visits, and a 19% reduction in physician visits in the case group after initiation of inhaled corticosteroids. In the control group, an increase of 34% in the number of outpatient visits occurred in the second year. All the decreases and increases were statistically significant. Children with regular patterns of inhaled corticosteroid refills were found to be significantly lower costing for Medicaid. However, after adjusting for potential confounders, no significant change in health care costs per asthmatic child occurred as a result of the introduction of inhaled corticosteroid therapy.
CONCLUSION: Overall, the study found that introduction of inhaled corticosteroids in a cohort of asthmatic children enrolled in Medicaid was beneficial to Medicaid because it brought about dramatic decreases in health care utilization without additionally increasing costs. 相似文献
METHODS: The North Carolina Medicaid claims database was used to retrieve clinical and economic variables for the purpose of this study. The case group, which was comprised of 84 children who started corticosteroid inhaler therapy between March 1994 and March 1995, was followed up for 1 year before and 1 year after the start of the therapy. The control group was comprised of 72 children with similar severity of asthma who remained on any other therapy other than corticosteroids for a continuous 2-year period. Paired t-tests were used to compare differences, and multiple regression analysis was used to adjust for potential confounders.
RESULTS: There was a 58% reduction in hospital visits, and a 19% reduction in physician visits in the case group after initiation of inhaled corticosteroids. In the control group, an increase of 34% in the number of outpatient visits occurred in the second year. All the decreases and increases were statistically significant. Children with regular patterns of inhaled corticosteroid refills were found to be significantly lower costing for Medicaid. However, after adjusting for potential confounders, no significant change in health care costs per asthmatic child occurred as a result of the introduction of inhaled corticosteroid therapy.
CONCLUSION: Overall, the study found that introduction of inhaled corticosteroids in a cohort of asthmatic children enrolled in Medicaid was beneficial to Medicaid because it brought about dramatic decreases in health care utilization without additionally increasing costs. 相似文献
54.
K. Fink M. Blohm G. Molderings H. Bönisch M. Göthert 《Naunyn-Schmiedeberg's archives of pharmacology》1992,345(6):633-638
Summary The effect of DSP4-induced destruction of noradrenergic neurones on 3H-3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (3H-CPP) binding to N-methyl-D-aspartate (NMDA) receptors and on 3H-desipramine (3H-DMI) binding to the neuronal noradrenaline carrier was investigated in rat brain cortex buffy coat membranes. 3H-DMI bound with high affinity to a single site at the neuronal noradrenaline carrier (KD = 5.26 ± 1.67 nmol/l) whereas the binding of 3H-CPP to the NMDA receptor was of intermediate affinity (KD = 274 ± 45 nmol/l). Fourteen days after a single-dose treatment with DSP4 (1) the Bmax value for 3H-DMI binding was reduced by 74%, (2) the Bmax value for 3H-CPP binding only tended to be decreased (by 24%; not statistically significant), (3) the endogenous noradrenaline content was reduced by 70% compared to untreated controls and, (4) the absolute amount of the NMDA-evoked 3H-noradrenaline overflow but not the fractional release was reduced by 55%. It is concluded that in the rat cerebral cortex presynaptic NMDA-receptors on noradrenergic nerve endings, which have previously been detected in release experiments with NMDA on cortical synaptosomes preincubated with 3H-noradrenaline, cannot be identified in radioligand binding experiments. Obviously, the cerebral cortical NMDA receptors are predominantly located on postsynaptic neuronal membranes and potentially on non-noradrenergic nerve terminals as well.Send offprint requests to M. Gothert at the above address 相似文献
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58.
JH Raphael JL Southall TV Gnanadurai GJ Treharne GD Kitas 《BMC musculoskeletal disorders》2002,3(1):17-8
Background
Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery. 相似文献59.
Inhibition of noradrenaline release in the rat vena cava via prostanoid receptors of the EP3-subtype. 下载免费PDF全文
1. In segments of the rat vena cava preincubated with [3H]-noradrenaline and superfused with physiological salt solution (containing desipramine and corticosterone), we studied the effects of prostaglandins of the D, E and F series, of a prostacyclin analogue and a thromboxane-mimetic and of subtype-selective prostaglandin E-receptor (EP-receptor) ligands on the electrically (0.66 Hz)-evoked tritium overflow. 2. The electrically-evoked tritium overflow was inhibited by prostaglandin E2 (maximum inhibition by about 80%; pIC40 7.49). The effect of prostaglandin E2 was not affected by rauwolscine, which, by itself, increased the evoked overflow; the alpha 2-adrenoceptor antagonist was added to the superfusion medium in all subsequent experiments. Indomethacin failed to affect either the evoked tritium overflow or its inhibition by prostaglandin E2. 3. The inhibitory effect of prostaglandin E2 on the electrically-evoked tritium overflow was not altered by the EP1-receptor antagonist. AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) at a concentration at least 30 fold higher than its pA2 value at EP1-receptors. The following compounds mimicked the effect of prostaglandin E2 showing the following rank order of potencies: misoprostol (EP2-/EP3-receptor agonist) congruent to sulprostone (EP1-/EP3-receptor agonist) congruent to prostaglandin E1 = prostaglandin E2 > iloprost (EP1-/IP-receptor agonist) = prostaglandin F2 alpha. The evoked overflow was not affected by high concentrations of prostaglandin D2 or the thromboxane-mimetic U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxy-methano-prostaglandin F2 alpha). 4. The present results suggest that the postganglionic sympathetic nerve fibres innervating the rat vena cava are endowed with presynaptic EP3-receptors.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
60.
Efficacy study of the small-bowel examination 总被引:8,自引:0,他引:8