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81.
Summary Cyclic adenosine 3,5monophosphate (cAMP) was assayed in CSF and plasma obtained from patients with multiple sclerosis. Decreased CSF cAMP levels were found in more than half of the patients while plasma cAMP was normal. The decrease is correlated significantly with the disability of the patient and with the progression of the disease. A low CSF cAMP level can be considered as prognostically unfavorable, particularly in the early stage of the disease. There was no correlation between the cAMP levels and the duration of the disease or with bouts and remissions. ACTH therapy did not normalize the decreased values. Obviously the decrease of CSF cAMP is related to the demyelination and not to the intensity of the pathological immunoreactions.
Zusammenfassung Es wurde das cyclische Adenosin-3,5monophosphat im Liquor von Patienten mit multipler Sklerose untersucht. Bei einem Teil der Patienten wurden auch die Vergleichswerte im Blutplasma bestimmt. Es zeigte sich bei mehr als der Hälfte der Patienten eine Verminderung der cAMP-Konzentration im Liquor bei normalem Plasmaspiegel. Diese cAMP-Verminderung erwies sich als signifikant abhängig von dem Schweregrad der Erkrankung bzw. der Erkrankungsprogredienz und ist besonders in frühen Erkrankungsfällen als prognostisch ungünstiges Zeichen anzusehen. Es fand sich kein Zusammenhang mit dem Krankheitsstadium, d.h. Schub bzw. Intervall, und mit der Erkrankungsdauer. Eine ACTH-Behandlung vermochte diese Verminderung der Werte nicht auszugleichen. Es wird die Wertigkeit dieser Befunde diskutiert.相似文献
82.
E. Leung K. A. Jacobson R. D. Green 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(6):639-644
Summary While G protein-coupled receptors are often studied by analyzing antagonist radioligand: cold agonist inhibition curves using an independent site model, it is now clear that KL and KH values determined in these analyses are not reliable estimates of the affinities of the agonists for free and G protein-coupled forms of the receptor. Thus, such experiments cannot be used to contrast the characteristics of a given type of receptor in different tissues, i.e., to probe for the existence of receptor subtypes. Since treatment with N-ethylmaleimide treatment blocks receptor: Gi/G0 protein interactions, such analyses on N-ethylmaleimide-pretreated membranes should allow direct assessment of the affinities of competing ligands for the free receptor or for multiple receptor subtypes.As A1 adenosine receptors couple to Gi, and perhaps to Go, we have performed A1 adenosine receptor radio-ligand competition studies first on control, then on N-ethylmaleimide-pretreated bovine cardiac and cerebral cortical membranes. Results of experiments with the antagonist radioligand [3H]xanthine amine congener appeared to be confounded by ligand binding to A2 adenosine receptors present in the cardiac membrane preparations. Further experiments utilized the A1-specific radioligand [3H] 1,3-dipropyl-8-cyclopentylxanthine. These experiments confirmed once more that the KL values determined by computer analysis of competition curves performed on control membranes are not reliable estimates of the affinities of the competing ligand for free receptors. Furthermore the results supported the hypothesis that similar analyses on NEM-treated membranes provide reliable estimates of the affinity(s) of competing ligands for free receptors. Lastly, the results suggest that cardiac membranes contain two subtypes of A1 adenosine receptors that are differentiated by 5-modified but not N6-modified adenosine analogs. One of these receptor subtypes appears to be the same as the A1 receptor detected in cortical membranes.Abbreviations [125I]ABA
[1251](N6-p-aminobenzyl)adenosine
- [3H]CPX
[3H]8-cyclopentyl-1,3-dipropylxanthine
- [3H]R-PIA
[3H]N6-R-phenylisopropyladenosine
- [6H]XAC
[6H]xanthine amine congener
- CHA
N6-cyclohexyladenosine
- EDTA
ethylenediaminetetraacetic acid
- [125I]BW-A844U
[125I]3-(4-amino)phenethyl-l-propyl-8-cyclopentylxanthine
- NCCA
5-N-cyclopropylcarboxamide adenosine
- NECA
5-N-ethylcarboxamide adenosine
- PMSF
phenylmethylsulphonyl fluoride
- NEM
N-ethylmaleimide
Recipient of a Postdoctoral Fellowship from the Chicago Heart Association 相似文献
83.
H. Fuder A. Brink M. Meincke U. Tauber 《Naunyn-Schmiedeberg's archives of pharmacology》1992,345(4):417-423
Summary To investigate whether endogenous purinoceptor agonists affect the sympathetic neurotransmission in the rat isolated iris, and to classify the purinoceptors modulating exocytotic [3H]-noradrenaline release, we have determined the effect of adenosine receptor antagonists on, and the relative potency of selected agonists in modulating, the field stimulation-evoked (3 Hz, 2 min) [3H]-noradrenaline overflow. In addition, the apparent affinity constants of 8-phenyltheophylline (8-PT) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in antagonizing the prejunctional effects of purinoceptor agonists were estimated.The relatively A1-selective DPCPX 10 and 100 nmol/l increased the evoked [3H]-noradrenaline overflow by about 25%–35%a indicating a minor inhibition of evoked release by endogenous purinoceptor agonists probably via an A1 adenosine receptor. Whereas the A1/A2-antagonist 8-PT failed to increase the evoked [3H]-noradrenaline overflow in the absence of exogenous agonists (without or with dipyridamole 1 pmol/l present), the relatively A2-selective antagonist CP-66,713 (4-amino-8-chloro -1-phenyl(1,2,4)triazolo(4,3-a)quinoxaline) 100 nmol/l decreased it by 20%–30% in the absence and continuous presence of DPCPX. This may be compatible with a minor A2-mediated facilitation by an endogenous purinoceptor agonist.All exogenous agonists tested (except UTP 100 mol/l) inhibited the evoked [3H]-noradrenaline overflow. The relative order of agonist potency (IC4o, concentration in mol/l for inhibition of evoked release by 40%) was CPA (N6-(cyclopentyl)adenosine, 0.004) > R-PIA (R(–)N6-(2phenylisopropyl)adenosine, 0.066) = CHA (N6-(cyclohexyl)adenosine, 0.082) > NECA (N5-(ethyl-carboxamido)adenosine 0.44) > ADO (adenosine, 4.1). ATP was n early equipotent with ADO. Maximum inhibition was 70%–80% and similar for all agonists. Adenosine deaminase 1 u/ml failed to affect the ATP-induced, but abolished the adenosine-induced prejunctional inhibition. The adenosine uptake inhibitor S-p-nitrobenzyl-6-thioguanosine (NBTG) failed to enhance the potency of ADO and ATP. The A1-selective antagonist DPCPX 10 nmol/l did not reduce the ATP potency indicating an effect of ATP per se not mediated via an A1 purinoceptor.Prejunctional affinity constants of 8-PT were 6.07 when tested against adenosine (in the presence of dipyridamole), and 6.60 against CHA. The apparent -log KB of DPCPX tested against CPA was 9.71. The high DPCPX affinity is compatible with an A1 adenosine receptor mediating inhibition of sympathetic neurotransmission in rat iris. This receptor may not be the only prejunctional purinoceptor on rat iris sympathetic nerves. The receptor by which ATP acts prejunctionally in this tissue remains to be determined.This study was supported by the Deutsche Forschungsgemeinschaft (Fu 163/2 and 163/3)
Send offprint requests to H. Fuder at the above address 相似文献
84.
Adenosine is recognized as an important modulator of cell activity. In particular, adenosine regulates the secretion of adrenocorticotropin from anterior pituitary cells. However, the possible role of adenosine on the pars intermedia has never been investigated. In the present study, we have examined the effect of adenosine on α-melanotropin (α-MSH) secretion from the intermediate lobe of the pituitary of the frog (Rana ridibunda), using the perifusion technique. When whole neurointermediate lobes were exposed to graded doses of adenosine (10(-9) to 10(-4) M), a dose-dependent inhibition of a-MSH release was observed. Repeated pulses of adenosine (5 ± 10(-5) M) induced a reproducible inhibition of α-MSH secretion without any desensitization phenomenon. The effect of adenosine was mimicked by the non-selective agonist 5'-N-ethylcarboxamide-adenosine and the highly specific adenosine A, receptor agonist N(6) -[R-phenylisopropyl]-adenosine (R-PIA). In contrast the selective adenosine A(2) receptor agonist, CGS 21680, induced a slight stimulation of α-MSH release. Adenosine-induced inhibition of α-MSH secretion was blocked by the non-selective adenosine antagonist, 8-(p-sulfophenyl)-theophyline. Adenosine and R-PIA also inhibited α-MSH secretion from acutely dispersed pars intermedia cells. Adenosine did not block thyrotropin-releasing hormone-induced α-MSH release from perifused neurointermediate lobes. In contrast, adenosine inhibited both acetylcholine-evoked and muscarine-evoked α-MSH secretion. Finally, R-PIA induced a significant inhibition of basal and forskolin-stimulated cyclic AMP levels in whole neurointermediate lobes. The present results demonstrate that adenosine exerts a direct inhibitory effect on α-MSH release from melanotrope cells through activation of the A(1) receptor subtype, negatively coupled to adenylate cyclase. These data suggest that adenosine may play a physiological role in the regulation of hormone release from the intermediate lobe of the pituitary. 相似文献
85.
Stephen J. Gallacher William D. Fraser Fraser C. Logue Frances J. Dryburgh Robert A. Cowan Iain T. Boyle Stuart H. Ralston 《Calcified tissue international》1992,51(6):419-423
Summary In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n=13), 45 mg (n=9), and 90 mg (n=13) in an attempt to see what factors influenced the response of serum calcium to pamidronate.The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into good and poor responders depending on whether a normal serum calcium was obtained.Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r=0.45, P=0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean±SEM): 65.0±9.4 nmol/liter GF (poor responders) versus 29.6±6.3 (good responders), P=0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r=-0.41, P=0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF±0.09 (poor responders) versus 0.76 mmol/liter GF±0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response. A significant negative correlation was evident between NcAMP and TmPO4 (r=-0.35, P=0.003), however, no significant correlation was evident between NcAMP and TmCa or TmPO4 and TmCa.These results suggest that in a hypercalcemic patient where evidence exists for the presence in circulation of a factor with PTH-like activity (i.e., NcAMP is elevated or TmPO4 is low) the response of serum calcium to pamidronate is less good. NcAMP would appear to be a useful predictor of the response of serum calcium, whereas TmPO4 is less discriminating. 相似文献
86.
Delumeau JC Tencé M Marin P Cordier J Glowinski J Prémont J 《The European journal of neuroscience》1991,3(6):539-550
Adenosine has a broad array of actions on neurons but astrocytes also possess adenosine receptors. We have previously shown that adenosine, by acting on astrocytes in the striatum, can modulate neuronal responses mediated by receptors coupled to phospholipase C through an astrocyto - neuronal interaction. In addition, adenosine was found to potentiate the alpha1-adrenergic production of inositol phosphates in astrocytes. The mechanism involved in this potentiation was further investigated by examining the effects of adenosine and alpha1-adrenergic receptor agonists on cytosolic Ca2+ in cultured striatal astrocytes from the embryonic mouse in primary culture. When used alone, methoxamine, a selective agonist of alpha-adrenergic receptors or 2-chloroadenosine, a stable analogue of adenosine, induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+, which seems to be due to a Ca2+ influx, because it was not observed in the absence of external Ca2+. Voltage independent Ca2+ channels contribute to this process and different blockers of voltage-operated calcium channels, such as dihydropyridines, phenylalkylamines, La3+ or Co2+ were ineffective in suppressing the sustained cytosolic Ca2+ elevation. Three observations suggest the implication of arachidonic acid in the observed potentiation: (i) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the coapplication of methoxamine and 2-chloroadenosine; (ii) the addition of arachidonic acid during the calcic plateau produced by the combined application of the agonists did not increase further cytosolic Ca2+ levels; (iii) in the presence of methoxamine, 2-chloroadenosine induced a release of arachidonic acid. The stimulation of phospholipase C and the resulting activation of protein kinase C induced by methoxamine seem to be required for the potentiating effect of 2-chloroadenosine on cytosolic Ca2+. In fact, the direct activation of protein kinase C by an exogenous diacylglycerol analogue mimicked the effect of methoxamine because, in this condition, 2-chloroadenosine alone evoked a sustained elevation of cytosolic Ca2+. Therefore, methoxamine, through the successive activation of phospholipase C and protein kinase C, could allow a lipase, probably phospholipase A2, to be stimulated by 2-chloroadenosine. Arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates in other cell types. Therefore, in striatal astrocytes, 2-chloroadenosine, through an arachidonic acid-mediated hyperpolarization, could increase the Ca2+ driving force and thus improve Ca2+ influx through inositol phosphate-gated channels. This hypothesis is further supported by the suppressing effect of a 50 mM KCI-induced depolarization on the long lasting elevation of cytosolic Ca2+ seen in the combined presence of 2-chloroadenosine and methoxamine. 相似文献
87.
Summary The reactions of adenosine 14C- and 32P-labelled ATP with isolated membranes from catecholamine storage vesicles of the bovine adrenal medulla were studied. In presence of Mg2+ about twice as much of 32P-radioactivity combined with the membrane as 14C-adenosine compounds at 31°C and also at 0°C, while in the absence of Mg2+ the amounts of 14C and 32P incorporated were similar for both substances. Autoradiography of the SDS-polyacrylamide gel after electrophoresis of the 32P-ATP-treated membrane protein showed two distinct zones corresponding to protein bands. Sonication released twice as much 32P-ATP as 14C-ATP from the space within the membrane particles indicating that at least half of the ATP present in this space did not contain its original terminal phosphate group. About 40–45% of the 32P-radioactivity was incorporated in the membrane lipids, whereas only small amounts of 14C-radioactivity were extracted with the lipids. About 1/3 of the incorporated 14C-radioactivity was not extractable with acids. The same amount remained in the 32P-ATP treated preparation acid-stably bound after extraction of the lipids and thus must be firmly bound ATP. When the reaction of the membrane preparation with labelled ATP was performed at 0°C the fractions of the acid-stably bound 32P- and 14C-radioactivity increased. About 1 nmole/mg of protein (10–15%) of the bound 32P-radioactivity was exchangeable against unlabelled ATP, while only a very small fraction (<0.5 nmole/mg protein) of the 14C-radioactivity was exchanged against unlabelled ATP. Preincubation of the membrane particles with ATP-Mg2+ at 0°C induced 30% inhibition of the ATPase activity and abolition of the net uptake of catecholamines. Different K
m
values obtained from initial velocity studies of ATPase activity and the overall-incorporation of 32P-radioactivity indicated that a direct correlation between these processes did not exist. Different strong inhibitory effects exerted by ADP on the ATPase activity and net uptake of catecholamine at the one hand and the overall 32P- and 14C-incorporation at the other hand supported that view. It is concluded that only small fractions of the observed 32P-and 14C-incorporation can be involved in the ATP-hydrolyzing reaction. 相似文献
88.
卡托普利对病毒性心肌炎小鼠心肌线粒体结构及其酶活性的影响 总被引:1,自引:2,他引:1
目的 研究卡托普利对病毒性心肌炎小鼠心肌线粒体结构和三磷酸腺苷 (ATP)酶活性变化的影响。方法 将雄性Balb/c小鼠随机分为柯萨奇病毒B3 (CVB3 )感染组、CVB3 感染加卡托普利治疗组和对照组。以d3、d14为两个时相点 ,比较线粒体超微结构 ,线粒体Na+ K+ ATP酶、Ca2 + ATP酶活性变化。结果 感染组心肌细胞线粒体结构破坏 ,线粒体Na+ K+ ATP酶、Ca2 + ATP酶活性较对照组显著下降 (P均 <0 .0 1)。卡托普利治疗组各时相点线粒体结构破坏较轻 ,线粒体Na+ K+ATP 酶、Ca2 + ATP酶活性较感染组明显增高 (P均 <0 .0 5 )。结论 病毒性心肌炎早期即可见心肌线粒体结构破坏 ,ATP酶活性下降。卡托普利可有效保护心肌线粒体结构和功能 相似文献
89.
高效毛细管电泳法同时测定红花中腺苷、芦丁和槲皮素的含量 总被引:19,自引:0,他引:19
目的 用高效毛细管电泳法对红花中的有效成分腺苷、槲皮素和芦丁同时进行含量测定。方法 采用熔融石英毛细管柱(66.5 cm×50 μm ID,有效长度58 cm)作为分离通道;以50 mmol·L-1硼砂其中含18%甲醇的溶液(pH 9.7)为运行缓冲液;运行电压: 24 kV;毛细管柱温: 20 ℃;检测波长: 210 nm。结果 以利福平为内标,腺苷、芦丁和槲皮素分别在10~160 mg·L-1,100~2 000 mg·L-1和100~1 600 mg·L-1 线性关系良好(R>0.998);平均回收率分别为98.5%~100.5%, 96.9%~99.5%和99.1%~99.5%; RSD分别为6.5%,5.2%和5.6%(N=5)。结论 此法操作简便快速,回收率及重现性好,可作为红花质量控制的方法。 相似文献
90.
腺苷A1受体阻断剂对学习记忆的影响及机制分析腺苷A1受体阻断剂对学习记忆的影响及机制分析 总被引:2,自引:0,他引:2
目的探讨腺苷A1受体阻断剂对学习记忆的影响及其与胆碱能、氨基酸能神经的关系。方法采用避暗实验、分光光度法和HPLC法,观察腺苷A1受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)对东莨菪碱(Scop)、2-氨基-5-磷戊酸(AP5)致小鼠记忆障碍及脑胆碱酯酶(AChE)活性、氨基酸水平的影响。结果DPCPX可显著改善Scop致记忆障碍,但对AP5致记忆障碍无影响;在体内外高剂量DPCPX可显著抑制小鼠脑AChE活性;DPCPX icv可显著升高小鼠脑Glu和Asp含量,降低GABA含量,使脑内Glu/GABA比值显著升高。结论腺苷A1受体特异性阻断剂DPCPX可显著改善Scop而不能改善AP5致记忆障碍,在高剂量时可影响脑AChE活性和脑氨基酸水平、升高脑内Glu/GABA比值。 相似文献