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81.
Kenichiro Mikawa Hiroaki Kume Kenzo Takagi 《Clinical and experimental pharmacology & physiology》1997,24(2):175-181
1. In order to examine the mechanisms of cGMP-induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8-brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca2+ concentrations were studied by measuring the spectra of fura-2 loaded in guinea-pig tracheal strips. 2. Atrial natriuretic peptide and 8-brom cGMP caused a concentration-dependent inhibition of spontaneous tone in the guinea-pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large-conductance Ca2+-activated K+ (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8-brom cGMP and augmented EC70 values for ANP and EC50values for 8-brom cGMP approximately 27- and 17-fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage-operated Ca2+channels (VOCC). 3. The inhibitory action of ANP and 8-brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP-sensitive K+ channels, and 100 nmol/L apamin, an inhibitor of small-conductance Ca2+-activated K+ channels. When these agents were applied to tissues precontracted by high (40mmol/L) K+, the relaxant effects of these agents markedly diminished. 4. The extracellular Ca2+-dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8-brom cGMP. Concentration—response curves to extracellular Ca2+ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca2+ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca2+ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca2+ by ANP was suppressed. 6. We conclude that ANP and 8-brom cGMP activate BKca channels and that the inhibition of Ca2+ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP-dependent bronchodilation. 相似文献
82.
单波长荧光分光光度计测定细胞内Ca^2+浓度的方法探索 总被引:2,自引:1,他引:1
在使用单波长荧光分光光度计测定细胞内游离钙浓度时,通过快速(4~6s)手动转换激发波长(EX),分别测定EX340和380nm时的荧光强度变化,并计算出340nm与380nm时的荧光强度比率(R),然后也采用双波长荧光分光光度计测定细胞内Ca2+浓度的计算公式计算细胞内游离钙浓度。结果显示单波长荧光分光光度计按比例法测得的细胞内游离Ca2+浓度与使用双波长荧光分光光度计测得的结果相似。 相似文献
83.
Using the whole-cell configuration of the patch clamp technique, calcium-activated potassium currents (IK,Ca) were investigated in ramified murine brain macrophages. In order to induce IK,Ca the intracellular concentration of nominal free Ca2+ was adjusted to 1μM. The Ca2+-activated K+ current of brain macrophages did not show any voltage dependence at test potentials between –120 and +30mV. A tenfold change
in extracellular K+ concentration shifted the reversal potential of IK,Ca by 51mV. The bee venom toxin apamin applied at concentrations of up to 1μM did not affect IK,Ca. Ca2+-activated K+ currents of ramified brain macrophages were highly sensitive to extracellularly applied charybdotoxin (CTX). The half-maximal
effective concentration of CTX was calculated to be 4.3nM. In contrast to CTX, the scorpion toxin kaliotoxin did not inhibit
IK,Ca at concentrations between 1 and 50nM. Tetraethylammonium (TEA) blocked 8.0% of IK,Ca at a concentration of 1mM, whereas 31.4% of current was blocked by 10mM TEA. Several inorganic polyvalent cations were tested
at a concentration of 2mM for their ability to block IK,Ca. La3+ reduced IK,Ca by 72.8%, whereas Cd2+ decreased IK,Ca by 17.4%; in contrast, Ni2+ did not have any effect on IK,Ca. Ba2+ applied at a concentration of 1mM reduced IK,Ca voltage-dependently at hyperpolarizing potentials.
Received: 17 January / Accepted: 5 May 1997 相似文献
84.
Jaafar Mouhyi Lars Sennerby Jeanjacques Pireaux Nicolas Dourov Samir Nammour Jack Van Reck 《Clinical oral implants research》1998,9(3):185-194
The purpose of the present study was to analyse clinically failed and retrieved implants prior to and after cleaning by means of scanning electron microscopy (SEM) and X-ray induced photoelectron spectroscopy (XPS) as compared to unused controls. Six different chemical and physical techniques for cleaning of contaminated titanium implants were evaluated: 1) rinsing in absolute ethanol for 10 min, 2) cleaning in ultrasonic baths containing trichloroethylene (TRI) and absolute ethanol, 10 min in each solution, 3) abrasive cleaning for 30 s, 4) cleaning in supersaturated citric acid for 30 s, 5) cleaning with continuous CO2-laser in dry conditions at 5 W for 10 s, 6) cleaning with continuous CO2-laser in wet conditions (saline) at 5 W for 10 s. SEM of failed implants showed the presence of contaminants of varying sizes and XPS showed almost no titanium but high carbon signals. XPS of unused titanium implants showed lower levels of titanium as previously reported, probably due to contamination of carbon which increased with time in room air. Cleaning of used implants in citric acid followed by rinsing with deionized water for 5 min followed by cleaning in ultrasonic baths with TRI and absolute ethanol gave the best results with regard to macroscopical appearance and surface composition. However, as compared to the unused implants the results from an element composition point of view were still unsatisfactory. It is concluded that further development and testing of techniques for cleaning of organically contaminated titanium is needed. 相似文献
85.
Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine 总被引:1,自引:0,他引:1
L. C. Kirkwood R. L. Nation & A. A. Somogyi 《British journal of clinical pharmacology》1997,44(6):549-555
Aims Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated.
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K m values. The kinetic constants for O -demethylation were significantly different in extensive and poor metabolizers. The extensive metabolizers had a mean intrinsic clearance to dihydromorphine more than ten times greater than the poor metabolizer. The CYP2D6 chemical inhibitors, quinidine and quinine, and LKM1 antibodies inhibited O -demethylation in extensive metabolizers; no effect was observed in microsomes from a poor metabolizer.
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
86.
硒和/或维生素E预防大鼠内皮细胞损伤的实验研究 总被引:15,自引:1,他引:14
用含硒(Se0.5mg/kg)和/或维生素E(VE0.6g/kg)的高脂饲料喂养成年雄性Wistar大鼠12周。结果:高脂对照组大鼠血浆前列腺素Flα(6-酮-PGF1α)水平下降,而血清脂质过氧化物(LPO)、血浆血栓素(TXB2)及内皮素(ET)水平上升;补Se、VE及Se+VE可明显降低大鼠血清LPO、血浆TXB2、ET及TXB2/6-酮-PGF1α比值。同时,除了明显提高血浆谷胱甘肽过氧化物酶(GSH-Px)活力外,血浆6-酮-PGF1α浓度明显升高。实验提示,Se和/或VE有调节花生四烯酸代谢及保护内皮细胞的作用。 相似文献
87.
The effect of Cyclosporin A (CsA) on prostaglandin E2 (PGE2 ) production in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-α) was studied. TNF-α (1-100 ng/ml) dose-dependently stimulated PGE2 ; formation in 24 h cultures. CsA (1-100 ng/ml) did not induce PGE2 ; formation itself but potentiated TNF-α induced PGE; formation in gingival fibroblasts in a manner dependent on the concentrations of both CsA and TNF-α. TNF-α (10 ng/ml) stimulated the release of [3 H]-arachidonic acid (A.A) from prelabelled fibroblasts that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5-20 μM/ml) to the cells resulted in enhanced PGE2 : formation that was not potentiated by CsA (100 ng/mi). Furthermore. CsA (100 ng/ml) did not further increase the level of cyclooxygenase-2 mRNA induced by TNF-α (10 ng/ml). although PGE2 formation was enhanced. The results indicate that CsA and TNF-α act in concert on PGE2 formation in gingival fibroblasts. which may be of importance in the pathogenesis of gingival overgrowth induced by the drug. 相似文献
88.
I. Hilakivi L. Ahtee J. O. Rinne T. Taira L. M. J. Attila P. Marjamäki 《Journal of neural transmission (Vienna, Austria : 1996)》1995,102(2):139-148
Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither3[H]SCH 23390 nor3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus. 相似文献
89.
Alpha2-HS glycoprotein phenotypes and quantitative hormone and bone measures in postmenopausal women
June E. Eichner Christopher A. Friedrich Jane A. Cauley Mohammad I. Kamboh James P. Gutai Lewis H. Kuller Robert E. Ferrell 《Calcified tissue international》1990,47(6):345-349
Summary It has been suggested that inherited traits play a role in the development of osteoporosis by providing a background for the
modulation of gene expression. In this study, we examine the influence of the different alleles of alpha2-HS glycoprotein (AHSG), a protein of the bone matrix, on quantitative estrogens, estrone and estradiol, and bone measures,
bone area and density. Estrogens provide a protective effect against fractures in older women and were thus included in the
analyses. Isoelectric focusing of AHSG from sera followed by immunoblotting was used to type 163 white post-menopausal women
participating in a clinical trial of the effects of walking on bone loss. Plasma hormones were measured by a combination of
extraction, column chromatography, and radioimmunoassay; bone measures on the dominant radius were determined with computerized
tomography. Analysis of variance was done on estrogen and bone measures after controlling for the effects of age and body
mass index. The two major alleles of AHSG result in three phenotypes, designated AHSG 1-1, AHSG 2-1, and AHSG 2-2. The AHSG
1-1 homozygote showed a decreased concentration of estradiol, the AHSG 2-2 homozygote showed an increased concentration, and
the AHSG 2-1 heterozygote was intermediate (P=0.001). Estrone demonstrated a similar pattern in residual analysis although it did not reach statistical significance. 相似文献
90.