全文获取类型
收费全文 | 1280篇 |
免费 | 71篇 |
国内免费 | 72篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 54篇 |
妇产科学 | 11篇 |
基础医学 | 103篇 |
口腔科学 | 36篇 |
临床医学 | 159篇 |
内科学 | 494篇 |
皮肤病学 | 23篇 |
神经病学 | 9篇 |
特种医学 | 245篇 |
外科学 | 77篇 |
综合类 | 34篇 |
预防医学 | 25篇 |
眼科学 | 14篇 |
药学 | 91篇 |
肿瘤学 | 46篇 |
出版年
2021年 | 6篇 |
2016年 | 7篇 |
2015年 | 14篇 |
2014年 | 17篇 |
2013年 | 36篇 |
2012年 | 17篇 |
2011年 | 14篇 |
2010年 | 32篇 |
2009年 | 45篇 |
2008年 | 27篇 |
2007年 | 61篇 |
2006年 | 30篇 |
2005年 | 30篇 |
2004年 | 25篇 |
2003年 | 30篇 |
2002年 | 26篇 |
2001年 | 29篇 |
2000年 | 24篇 |
1999年 | 22篇 |
1998年 | 64篇 |
1997年 | 75篇 |
1996年 | 73篇 |
1995年 | 66篇 |
1994年 | 48篇 |
1993年 | 53篇 |
1992年 | 20篇 |
1991年 | 21篇 |
1990年 | 27篇 |
1989年 | 50篇 |
1988年 | 33篇 |
1987年 | 56篇 |
1986年 | 22篇 |
1985年 | 28篇 |
1984年 | 18篇 |
1983年 | 34篇 |
1982年 | 24篇 |
1981年 | 29篇 |
1980年 | 27篇 |
1979年 | 6篇 |
1978年 | 14篇 |
1977年 | 19篇 |
1976年 | 16篇 |
1975年 | 8篇 |
1974年 | 21篇 |
1973年 | 7篇 |
1972年 | 12篇 |
1971年 | 12篇 |
1970年 | 7篇 |
1969年 | 10篇 |
1967年 | 7篇 |
排序方式: 共有1423条查询结果,搜索用时 15 毫秒
31.
Expression of fibrinogen receptors during activation and subsequent desensitization of human platelets by epinephrine 总被引:2,自引:0,他引:2
Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The current studies were designed to examine the effect of occupancy of platelet alpha 2-adrenergic receptors by epinephrine on the expression of fibrinogen receptors and on the aggregation of platelets. The ability of epinephrine to induce the expression of fibrinogen receptors was studied under two different conditions: acute stimulation (less than 1 min) and prolonged stimulation (50 to 90 min), the latter of which is associated with a reduction or "desensitization" of the platelet aggregation response. Expression of the fibrinogen receptor was monitored with 125I-fibrinogen as well as with 125I-PAC-1 (PAC-1), a monoclonal antibody that binds to the glycoprotein IIb-IIIa complex only after platelets are activated. Epinephrine caused an immediate increase in PAC-1 and fibrinogen binding that was dependent on occupancy of the alpha 2-receptor by epinephrine and on the presence of extracellular free Ca (KCa = 30 mumol/L). By itself, 1 mmol/L Mg was unable to support induction of the fibrinogen receptor by epinephrine. However, it did decrease the Ca requirement by about two orders of magnitude. Prolonged stimulation of unstirred platelets by epinephrine led to a 70% decrease in the aggregation response when the platelets were subsequently stirred. Despite their decreased aggregation response, desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due simply to a decrease in fibrinogen receptor expression. Although desensitization was not affected by pretreatment of the platelets with aspirin, it was partially prevented when extracellular Ca was chelated by EDTA during the long incubation with epinephrine. These studies demonstrate that once platelet alpha 2-adrenergic receptors are occupied by epinephrine, extracellular Ca is involved in initiating the aggregation response by supporting the induction of the fibrinogen receptor and the binding of fibrinogen. Furthermore. Ca-dependent reactions subsequent to fibrinogen binding may be necessary for maximal platelet aggregation and are impaired when platelets become desensitized to epinephrine. 相似文献
32.
Role of prostaglandin and thromboxane biosynthesis in gastric necrosis produced by taurocholate and ethanol 总被引:2,自引:0,他引:2
Prof. Dr. S. J. Konturek T. Brzozowski I. Piastucki T. Radecki A. Dembińska-Kieć 《Digestive diseases and sciences》1983,28(2):154-160
The effects of a new selective inhibitor of thromboxane biosynthesis, OKY-1581, and a potent inhibitor of cyclooxygenase, indomethacin, on gastric mucosal lesions induced by taurocholate or ethanol and mucosal generation of prostaglandins have been studied in rats. OKY-1581 prevented, dose dependently, the formation of taurocholate- but not ethanol-induced gastric necrosis, and this effect was accompanied by an increase in gastric mucosal generation of prostaglandin E2 and I2-like activity and a reduction in the thromboxane generation during platelet aggregation. OKY-1581 enhanced the cytoprotective action of "mild" irritants such as 5 mM taurocholate against gastric damage by 100 mM taurocholate, whereas indomethacin produced opposite effects. This study indicates: (1) the inhibition of thromboxane biosynthesis results in increased generation of prostaglandins which seems to contribute to the gastric mucosal integrity and, (2) thromboxanes may be involved in the pathogenesis of taurocholate-induced gastric mucosal lesions. 相似文献
33.
Subtypes of muscarinic receptors in canine pancreatic secretion in vivo and in vitro 总被引:1,自引:0,他引:1
S J Konturek J Jaworek J Tasler M Cieszkowski N Yanaihara 《International journal of pancreatology》1987,2(1):11-22
In conscious dogs with esophageal, gastric and pancreatic fistulae, sham-feeding and meat feeding increased the pancreatic protein secretion to a peak, reaching about 39% and 69% of CCK8 maximum, and raised plasma pancreatic polypeptide (PP) levels. Pirenzepine given intravenously (i.v.) (30 nmol.kg-1 or 3 mumol.kg-1) reduced dose-dependently the pancreatic protein and plasma PP responses to sham-feeding and meat feeding, being about 100 times less potent as an inhibitor than atropine. Neither pirenzepine nor atropine affected near-maximal pancreatic bicarbonate and protein responses to secretin (164 pmol.kg-1.h-1) and CCK8 (170 pmol.kg-1.h-1), but both antimuscarinic agents significantly inhibited pancreatic responses to lower doses of these secretagogues. When added to the incubation medium of dispersed canine pancreatic acini, pirenzepine reduced dose-dependently the amylase responses only to urecholine, and not to CCK or gastrin, being about 1000 times less potent as an inhibitor than atropine. This report provides an evidence that pirenzepine inhibits pancreatic secretion in a similar manner to atropine, but that pirenzepine, in both in vivo and in vitro studies, is 2-3 orders of magnitude less potent as an inhibitor than atropine, indicating that the muscarinic pathway of the exocrine pancreas has a low affinity for pirenzepine and may thus involve M2-receptors. 相似文献
34.
Liu SC; Palek J; Yi SJ; Nichols PE; Derick LH; Chiou SS; Amato D; Corbett JD; Cho MR; Golan DE 《Blood》1995,86(1):349-358
Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation. 相似文献
35.
Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin 总被引:23,自引:3,他引:23
Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation. 相似文献
36.
O'Day SJ; Rabinowe SN; Neuberg D; Freedman AS; Soiffer RJ; Spector NA; Robertson MJ; Anderson K; Whelan M; Pesek K 《Blood》1994,83(9):2707-2714
Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity. 相似文献
37.
Sarah A Stuart Paul Butler Marcus R Munafò David J Nutt Emma SJ Robinson 《Neuropsychopharmacology》2015,40(9):2165-2174
The biochemical targets for antidepressants are relatively well established, but we lack a clear understanding of how actions at these proteins translate to clinical benefits. This study used a novel rodent assay to investigate how different antidepressant drugs act to modify affective biases that have been implicated in depression. In this bowl-digging task, rats encounter two equal value learning experiences on separate days (one during an affective manipulation and the other during control conditions). This induces an affective bias that is quantified using a preference test in which both digging substrates are presented together and the individual rats’ choices recorded. The assay can be used to measure affective biases associated with learning (when the treatment is given at the time of the experience) or examine the modification of previously acquired biases (when the treatment is administered before the preference test). The rapid-onset antidepressant ketamine, but not the delayed-onset antidepressant, venlafaxine, attenuated the previously acquired FG7142-induced negative bias following systemic administration. Venlafaxine but not ketamine induced a positive bias when administered before learning. We then used local drug infusions and excitotoxic lesions to localize the effects of ketamine to the medial prefrontal cortex and venlafaxine to the amygdala. Using a modified protocol we also showed that positive and negative biases amplified further when the numbers of substrate–reinforcer associations are increased. We propose that this pattern of results could explain the delayed onset of action of venlafaxine and the rapid onset of action but lack of long-term efficacy seen with ketamine. 相似文献
38.
The role of CGRP and afferent nerves in the modulation of pancreatic enzyme secretion in the rat 总被引:1,自引:0,他引:1
Jolanta Jaworek Stanisaw J. Konturek Aleksandra Szlachcic 《Journal of gastrointestinal cancer》1997,22(2):137-146
Summary
Conclusion Stimulation of pancreatic sensory nerves by capsaicin produced secretory effects probably caused, at least in part, by the
release of CGRP.
Background In the pancreas calcitonin gene-related peptide (CGRP) has been localized in the sensory nerves, but its physiological role
is unknown. This study was undertaken to compare the changes of pancreatic enzyme secretion produced by CGRP and by stimulation
or destruction of sensory nerves.
Methods To stimulate sensory nerves, low doses of capsaicin (0.25–0.5 mg/kg) were given intraduodenally to the conscious rats with
chronic pancreatic fistula. To inactivate sensory nerves high doses of capsaicin (100 mg/kg) were given subcutaneously 10
d before tests. For the in vitro experiments pancreatic slices and isolated pancreatic acini were prepared from intact and
capsaicin-denervated rats.
Results In conscious rats, CGRP given subcutaneously (5–10 μg/kg) and low doses of capsaicin given intraduodenally reduced basal pancreatic
secretion. In isolated pancreatic acini, CGRP (10−10–10−6
M), but not capsaicin, increased basal or secretagog-stimulated amylase release. In pancreatic slices (containing nerve fibers)
capsaicin (10−10–10−6
M) increased enzyme secretion, and this secretion was abolished by previous inactivation of sensory nerves by this neurotoxin.
Capsaicin deactivation did not affect the secretory response of pancreatic acini to CGRP, cerulein, or urecholine. Sensory
denervation by capsaicin did not change basal protein secretion, but reduced that produced by feeding or diversion of pancreatic
juice to the exterior during first 2 h of the tests. 相似文献
39.
40.
S J Konturek M E Kitler N Kwiecien W Obtulowicz J Oleksy B Kopp 《Scandinavian journal of gastroenterology》1984,19(8):1099-1103
The aim of this study was to assess the effects of a newly synthesized flavonoid, meciadanol, on gastric secretion and on aspirin-induced gastric mucosal injury in healthy humans. In vitro experiments have shown that meciadanol (INN proposed) inhibits histidine decarboxylase in gastric cells. In our study meciadanol did not affect either basal or pentagastrin-stimulated gastric acid secretion or pepsin secretion and did not produce any endoscopic or histological changes in the stomach or duodenum. Meciadanol prevented aspirin-induced microbleeding and aspirin-induced DNA loss, suggesting that gastric mucosal histamine is involved in the mucosal injury caused by aspirin. 相似文献