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101.
钙拮抗剂TMB-8抑制BHQ,NE和KCl引起的培养乳牛基底动脉单个平滑肌细胞内游离钙的升高 总被引:1,自引:0,他引:1
用AR CM MIC阳离子测定系统,测量单个细胞内游离钙浓度([Ca2+]i),研究8-(N,N-二乙胺)-n-辛基 3,4,5-三甲氧基苯甲酸酯(TMB-8)对培养乳牛基底动脉平滑肌[Ca2+]i的作用。在细胞外钙浓度为1.3mmol·L-1时,TMB-8(30μmol·L-1)可明显抑制BHQ,NE及KCl引起[Ca2+]i的升高。在细胞外钙为零+EGTA 0.1mmol·L-1时,TMB-8(10,30及100μmol·L-1)可浓度依赖性地降低静息[Ca2+]i,TMB-8(30μmol·L-1)可几乎完全阻断BHQ及NE引起[Ca2+]i的增加。研究表明TMB-8降低培养乳牛基底动脉平滑肌[Ca2+]i的机制,主要是抑制肌浆网Ca2+的释放,或增加肌浆网对Ca2+的摄入,并由此间接地抑制细胞外钙的内流。 相似文献
102.
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
103.
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
104.
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
105.
Elizabeth E. Epstein Barbara S. McCrady Linda S. Hirsch 《Alcoholism, clinical and experimental research》1997,21(3):547-556
Current knowledge about alcohol and marital functioning is limited by restrictive sample selection, inattention to the literature on individual-based alcoholic subtypes, and lack of research linking individual differences among alcoholics to marital functioning. The present study was designed to study marital functioning of alcoholics in light of current alcohol typologies. Subjects were part of a larger study on conjoint treatment of alcoholic males and their female partners. Four typologies—including Type 1/2, In-Home/Out-of-home, SteadyIEpisodic, and EarlyILate Onset—were tested for replicability and discriminant validity before linking them to marital functioning. Discriminant validity was found only for the Early (59%)-versus Late (41 %)-Onset typology; thus, further analyses linked only this typology with marital functioning. At baseline, Early-Onset couples reported more marital instability, and the females in these couples were more distressed. During treatment, Early-Onset couples reported higher daily marital satisfaction than Late-Onset couples. Regardless of age of onset, males reported higher marital satisfaction than their spouses during treatment, but their satisfaction did not increase during treatment. Female partners' marital satisfaction increased during treatment. Female partners of Late-Onset males reported particularly low marital satisfaction during treatment. Parsing the sample according to the early-/late-onset typology yielded different predictors of marital satisfaction for males and females within each subtype. For female partners of Early-Onset alcoholics, psychological distress unrelated to her pattner's drinking severity was most associated with her own marital satisfaction, whereas marital adjustment of female partners of Late-Onset alcoholics was most associated with the male's level of perceptual accuracy regarding her needs. This pattern was reversed for the males; marital adjustment of Early-Onset alcoholics was most associated with his partner's perceptual accuracy of his needs, whereas marital functioning of Late-Onset alcoholics was best accounted for by his own psychological distress. 相似文献
106.
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
107.
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
108.
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
109.
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
110.