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1.
S. L. Grant P. A. Phillips C. B. Gow 《Clinical and experimental pharmacology & physiology》1994,21(3):243-247
1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC50 2 ± 10?7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system. 相似文献
2.
Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans 总被引:1,自引:1,他引:0
P. M. Jones S. J. Persaud T. Bjaaland J. D. Pearson S. L. Howell 《Diabetologia》1992,35(11):1020-1027
Summary The involvement of nitric oxide as an intracellular messenger in the control of insulin secretion from pancreatic Beta cells was studied in rat islets of Langerhans by measuring: (i) nitric oxide generation in response to physiological insulin secretagogues; (ii) the effects of inhibitors of nitric oxide synthesis on insulin secretory responses to physiological secretagogues, and on insulin synthesis; (iii) changes in islet cyclic guanosine monophosphate in response to secretagogues; (iv) the effects of exogenous cyclic guanosine monophosphate and dibutyryl cyclic guanosine monophosphate on insulin secretion from electrically permeabilised islets and from intact islets, respectively. These studies produced no evidence that nitric oxide generation is required for the initiation of insulin secretion by common secretagogues. However, the results of our experiments suggest that the generation of nitric oxide may be involved in long-term, glucose-dependent increases in cyclic guanosine monophosphate content of islet cells, although the physiological relevance of these changes requires further investigation. 相似文献
3.
Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dtsz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder. 相似文献
4.
Decreased response of beta-adrenergic receptor has been considered to he one of the causes of increased responsiveness of the bronchi in asthma. Since beta-adrenergic receptor has two subtypes, beta1 and beta2 , and the bronchodilating effect of beta stimulants is mediated by beta2 -receptor, responsiveness of the bronchi is expected to correlate to the cyclic AMP response of lymphocytes to a beta2 -stimulant. Responsiveness of the bronchi was expressed as respiratory threshold to acetylcholine (RT-Ach), which was the minimal concentration of acetylcholine solution to cause an initial decrease of FEV1 of more than 20% of the baseline value. Beta1 and heta2 -responses were expressed as the increments of cyclic AMP content of 106 lymphocytes incubated with norepinephrine (beta1 -stimulant) and salbutamol (beta2 -stimulant).
RT-Ach showed a significant correlation with the beta2 -cyclic AMP response of lymphocytes, but not with the beta1 -response among patients with asthma. Sixteen symptomatic patients on continuous beta-stimulants showed lower RT-Ach value and diminished beta2 -receptor activity of lymphocytes compared with 14 patients in remission. These results suggest that selective beta2 -adrenergic blockade may he one of the causes of bronchial hypersensitivity in asthma, though it should be noted that in this study beta-adrenergic responses were examined in lymphocytes and were compared with the responsiveneness of the bronchi. Possible beta-receptor subsensitivity induced by administration of beta-stimulants is discussed. 相似文献
RT-Ach showed a significant correlation with the beta
5.
荷人鼻咽癌裸鼠血浆MDA,cAMP/cGMP水平及PSP的影响 总被引:2,自引:1,他引:2
本实验利用BALB/C裸小鼠,复制荷人鼻咽癌裸鼠模型,检测荷瘤鼠血浆丙二醛,cAMP,cGMP和cAMP/cGMP比值,观察云芝糖肽对荷人NPC裸鼠的抑瘤作用及对荷瘤鼠血浆MDA和cAMP/cGMP等的影响。结果发现荷瘤鼠血浆MDA升高,cAMP,cGMP降低,cAMP/cGMP比值升高,高你低浓度PSP对荷人NPC裸鼠均有明显抗癌作用(P<0.01),抑瘤率59.58-95.53%;并可降低荷瘤 相似文献
6.
Bâ A 《Developmental psychobiology》2005,47(4):408-414
Thiamine deficiency (B1 vitamin) was induced during three periods of rat central nervous system (CNS) ontogenesis. Females were fed a thiamine deficient diet such that developing offspring were exposed either to pre-, peri-, or postnatal thiamine deficiency. To control the effects of undernourishment generated by different thiamine deficiencies, every treatment group had its own pair-fed control pup from a non drug-treated but undernourished dam. Seven different developmental abilities (exploratory activity, emotional reaction, hind paws lifting reflex, wire grasping times, crawling and leap execution latencies, and nociception) were recorded in the offspring from the 10th to the 45th postnatal day. The vulnerability of developing brain to the specific lack of B1 vitamin increases from prenatal (28%) to perinatal (43%) and postnatal periods (57%). 相似文献
7.
Pre‐conditioning activates adenosine utilization in a cost‐effective way during myocardial ischaemia
G. Wikstrm M. Kavianipour G. Ronquist A. Waldenstrm 《Acta physiologica (Oxford, England)》2001,173(2):185-194
During pre‐conditioning the interstitial concentration of adenosine, in contrast to lactate, presents a die‐away curve‐pattern for every successive episode of ischaemia. This die‐away pattern might not necessarily be attributed to diminished adenosine production. The present study was undertaken to investigate whether pre‐conditioning alters the metabolic turnover of adenosine as observed by the lactate production during ischaemia. Interstitial levels of metabolites in pre‐conditioned (n=21) and non‐preconditioned (n=21) porcine hearts were monitored with microdialysis probes inserted in both ischaemic and non‐ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buffer containing adenosine (375 μM ), or buffer containing deoxyadenosine (375 μM ) were studied. All animals were subjected to 90 min of equilibrium microdialysis before 40 min of regional myocardial ischaemia and 120 min of reperfusion. Pre‐conditioning consisted of four repetitive episodes of 10 min of ischaemia and 20 min of reperfusion. Significantly higher levels of inosine and lactate were found in the ischaemic tissue of the pre‐conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgroups receiving deoxyadenosine and plain buffer, respectively. This difference was only valid for pre‐conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non‐preconditioned ischaemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non‐ischaemic myocardium baseline levels of metabolites were measured in all subgroups. Pre‐conditioning favoured degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the pre‐conditioned ischaemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5′‐triphosphate (ATP) investment. Utilization of adenosine in this way may also explain the successive die‐away pattern of adenosine seen in consecutive pre‐conditioning cycles. 相似文献
8.
家兔侧脑室内注射纯化内生致冷原(endogenous cryogen,EC)引起直肠温度下降和耳皮肤温度上升,其反应与静脉注射的情况相似,但直肠温度降低更加迅速,所用剂量仅为静脉注射达到同样效应时的1/80。静脉注射EC降温反应过程中,体温下降至最低点时脑脊液cAMP浓度显著下降,而cGMP浓度没有显著改变,血浆cAMP和cGMP浓度均显著升高;体温回升至正常水平时脑脊液、血浆cAMP和cGMP浓度均与对照组无显著差异。本实验结果提示:(1)EC的主要作用部位可能是中枢神经系统;(2)cAMP可能参与EC降温反应的中枢机制。 相似文献
9.
We examined the action of high (2×10–8M) and low (6×10–9M) concentrations of atrial natriuretic factor (ANF) on water and urea transport in the rat inner medullary collecting duct (IMCD) using the in vitro microperfusion technique. We measured the hydraulic conductivity (Lp ×10–6 cm/atm per second) and both lumen-to-bath (P
u(lb)) and bath-to-lumen (P
u(bl)) 14C-urea permeabilities (P
u× 10–5 cm/s) in the absence and in the presence of vasopressin (VP). High concentrations of ANF were able to inhibit the maximum activity of (50 U/ml) VP-stimulated L
p but physiological concentration of ANF inhibit only submaximum activity (10 U/ml) of VP-stimulated L
p. The hydrosmotic effect of dibutyryl-cyclic 3,5 adenosine monophosphate (cAMP) (10–4M) was unchanged by high concentrations of ANF (2×10–8M). Also we found that high (10–4M) and low (10–6M) concentrations of exogenous cyclic 3,5-guanosine monophosphate (GMP) while unable to change the Lp in the absence of VP, decreased the maximum activity of VP-stimulated Lp significantly. We also found that ANF inhibits partially and in a reversible manner the VP-stimulated P
u(lb) but not the VP-stimulated P
u(bl). These results demonstrated that plasma concentrations of ANF observed during volume expansion (10–10M) are able to inhibit submaximum activity of VP-stimulated (10 U/ml) L
p in the rat IMCD, this effect seems to occur before cAMP formation and it appears to be mediated by cGMP. ANF (6× 10–9M) also reduced the VP-stimulated urea outflux. Therefore, the increase in water excretion produced by ANF could be explained, at least in part, by the inhibition by ANF of vasopressin effects on water and urea transport in the IMCD.This study was presented in part at the VI Latin American Congress of Nephrology, Brazil, October 1985 and at the Xth International Congress of Nephrology, London, July 1987. 相似文献
10.
实验性过敏性哮喘豚鼠外周血液淋巴细胞β肾上腺素能受体系统的变化 总被引:1,自引:0,他引:1
在建立外周血液淋巴细胞β受体测定法的基础上,动态地观察了实验性过敏性哮喘豚鼠外周血液淋巴细胞中β受体最大结合容量(Bmax)、cAMP含量,以及血浆中儿茶酚胺(CA)含量的变化,发现它们都呈明显的时相性改变。通过分析它们发生的时间过程和相互关系,认为:在过敏性哮喘时所观察到的淋巴细胞β受体Bmax值的降低,乃是高水平内源性儿茶酚胺所致受体失敏的结果;并对所观察到的变化的意义作了初步探讨。 相似文献