全文获取类型
收费全文 | 1897篇 |
免费 | 153篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 39篇 |
儿科学 | 84篇 |
妇产科学 | 89篇 |
基础医学 | 323篇 |
口腔科学 | 33篇 |
临床医学 | 168篇 |
内科学 | 388篇 |
皮肤病学 | 24篇 |
神经病学 | 340篇 |
特种医学 | 22篇 |
外科学 | 175篇 |
综合类 | 8篇 |
预防医学 | 127篇 |
眼科学 | 31篇 |
药学 | 68篇 |
肿瘤学 | 137篇 |
出版年
2024年 | 5篇 |
2023年 | 26篇 |
2022年 | 36篇 |
2021年 | 85篇 |
2020年 | 55篇 |
2019年 | 79篇 |
2018年 | 77篇 |
2017年 | 69篇 |
2016年 | 75篇 |
2015年 | 69篇 |
2014年 | 96篇 |
2013年 | 98篇 |
2012年 | 150篇 |
2011年 | 155篇 |
2010年 | 73篇 |
2009年 | 86篇 |
2008年 | 111篇 |
2007年 | 131篇 |
2006年 | 121篇 |
2005年 | 102篇 |
2004年 | 85篇 |
2003年 | 81篇 |
2002年 | 61篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 9篇 |
1998年 | 15篇 |
1997年 | 12篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 15篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 2篇 |
1968年 | 1篇 |
1964年 | 2篇 |
排序方式: 共有2056条查询结果,搜索用时 250 毫秒
991.
992.
993.
Mohler EG Shacham S Noiman S Lezoualc'h F Robert S Gastineau M Rutkowski J Marantz Y Dumuis A Bockaert J Gold PE Ragozzino ME 《Neuropharmacology》2007,53(4):563-573
Recent evidence suggests that 5-hydroxytryptamine (5-HT)(4) receptor activity enhances cognition and provides neuroprotection. Here we report the effects of VRX-03011, a novel partial 5-HT(4) agonist, that is both potent (K(i) approximately 30 nM) and highly selective (K(i) > 5 microM for all other 5-HT receptors tested). In separate experiments, rats received VRX-03011 (0.1-10 mg/kg i.p.) 30 min prior to spontaneous alternation testing in a no-delay or a 30-s delay condition. VRX-03011 (1, 5 and 10 mg/kg, but not 0.1 mg/kg) significantly enhanced delayed spontaneous alternation performance while none of the doses enhanced performance in the no-delay test. VRX-03011 (1 and 5 mg/kg) concomitantly enhanced hippocampal acetylcholine output and delayed spontaneous alternation scores compared to that of vehicle controls, but had no effect on hippocampal acetylcholine release under a resting condition. Moreover, suboptimal doses of VRX-03011 and the acetylcholinesterase inhibitor galanthamine combined to enhance memory. VRX-03011 also regulated amyloid precursor protein (APP) metabolism by inducing a concentration-dependent increase in the non-amyloidogenic soluble form of APP (sAPPalpha) with an EC(50) approximately 1--10 nM. VRX-03011 had no effect on contractile properties in guinea pig ileum or colon preparations with an EC(50) > 10 microM and did not alter rat intestinal transit at doses up to 10 mg/kg. These findings suggest that VRX-03011 may represent a novel treatment for Alzheimer's disease that reduces cognitive impairments and provides neuroprotection without gastrointestinal side effects. 相似文献
994.
Cohen L Troub Y Turkov M Gilles N Ilan N Benveniste M Gordon D Gurevitz M 《Molecular pharmacology》2007,72(5):1220-1227
Among scorpion beta- and alpha-toxins that modify the activation and inactivation of voltage-gated sodium channels (Na(v)s), depressant beta-toxins have traditionally been classified as anti-insect selective on the basis of toxicity assays and lack of binding and effect on mammalian Na(v)s. Here we show that the depressant beta-toxins LqhIT2 and Lqh-dprIT3 from Leiurus quinquestriatus hebraeus (Lqh) bind with nanomolar affinity to receptor site 4 on rat skeletal muscle Na(v)s, but their effect on the gating properties can be viewed only after channel preconditioning, such as that rendered by a long depolarizing prepulse. This observation explains the lack of toxicity when depressant toxins are injected in mice. However, when the muscle channel rNa(v)1.4, expressed in Xenopus laevis oocytes, was modulated by the site 3 alpha-toxin LqhalphaIT, LqhIT2 was capable of inducing a negative shift in the voltage-dependence of activation after a short prepulse, as was shown for other beta-toxins. These unprecedented results suggest that depressant toxins may have a toxic impact on mammals in the context of the complete scorpion venom. To assess whether LqhIT2 and Lqh-dprIT3 interact with the insect and rat muscle channels in a similar manner, we examined the role of Glu24, a conserved "hot spot" at the bioactive surface of beta-toxins. Whereas substitutions E24A/N abolished the activity of both LqhIT2 and Lqh-dprIT3 at insect Na(v)s, they increased the affinity of the toxins for rat skeletal muscle channels. This result implies that depressant toxins interact differently with the two channel types and that substitution of Glu24 is essential for converting toxin selectivity. 相似文献
995.
Orr G Seidman SN Weiser M Gershon AA Dubrov Y Klein DF 《The Journal of nervous and mental disease》2008,196(6):496-500
Late onset dysthymic disorder (DD) in middle-aged and elderly men responds poorly to established antidepressants. Previous studies noted an improvement in mood accompanying sildenafil citrate treatment for erectile dysfunction. We sought to evaluate whether sildenafil's mood effects were independent of the effect on erectile function. A 6-week open label study was conducted with 20 male participants, aged 41-60 who were diagnosed with DD and who had normal erectile function. Participants were treated with sildenafil citrate 25 mg per day for 6 weeks. The primary outcome measure was the 21-item Hamilton Depression Rating Scale. Depressive and sexual symptoms were also evaluated using self-report questionnaires. Treatment with sildenafil resulted in a significant reduction in Hamilton Depression Rating Scale mean scores: from 14.61 +/- 3.5 at baseline to 6.39 +/- 5.13 at end of study (F(3,51) = 32.52, p = 0.001). No changes in sexual functioning were detected. Significant improvement was also noted on the self-report measures of depressive symptoms. Sildenafil citrate might have an antidepressant effect on late onset DD, that is not attributable to improvement in erectile function. Possible explanations for this effect are offered. Larger placebo controlled studies are warranted. 相似文献
996.
Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112–1120). Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivity — tremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivity — diaphoresis, fever, tachycardia and tachypnea; (c) altered mental status — agitation, excitement and, in advanced stages, confusion (Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434–441). It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors (Houlihan D. Serotonin syndrome resulting from coadministration of tramodol, venlafaxine, and mirtazapine. Ann Pharmacother 2004;38:411–413). The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112–1120). Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. The following case highlights the complex nature in which serotonin syndrome can arise, as well as the proper recognition and treatment of a potentially life-threatening yet easily avoidable condition. 相似文献
997.
998.
To reduce the overall time spent in the ED, triage nurses are encouraged to treat patients with a topical anesthetic cream, eutectic mixture of local anesthetics (EMLA). We present a case in which a 28-day-old neonate who was treated with EMLA cream in triage developed severe methemoglobinemia 18 hours post admission to the pediatric ward. This case demonstrates that there may be some risks associated with this approach, and that protocols for the use of EMLA at triage should include not only the indications for its use, but also need to ensure that there is a process to have the EMLA removed before patient discharge or transfer. 相似文献
999.
Pretransplant treatment of donors with immunomodulators to control graft-versus-host disease (GVHD) in transplant recipients 总被引:1,自引:0,他引:1
OBJECTIVE: Prevention of graft-versus-host disease (GVHD) by pretransplant donor treatment with known immunomodulators like complete Freund's adjuvant (CFA) and synthetic oligo-deoxynucleotides expressing CpG motifs (CpG). METHODS: Induction of GVHD by inoculation of C57BL/6 (C57) splenocytes into sublethally irradiated (BALB/c x C57BL/6) F1 (F1) mice. Splenocytes were derived from either naive C57 mice or from C57 mice that were treated previously with the immunomodulators. RESULTS: Inoculation of CFA or CpG into C57 mice led to an increase in the total number of spleen cells and resulted in activation of immunoregulatory cells that significantly suppressed mixed allogeneic lymphocyte reaction in vitro. CFA-treated C57 splenocytes led to GVHD-related death in only 14 out of 61 F1 recipients while the remaining 47 mice survived without disease for more than 200 days. Pretransplant treatment of donor C57 mice with GpG emulsified in incomplete Freund's adjuvant resulted in 19/20 GVHD-free survivors of sublethally irradiated F1 mice for more than 200 days. In contrast, naive C57 splenocytes injected into sublethally irradiated F1 recipients induced severe GVHD, which resulted in the death of 77/78 recipient mice (median of survival was 16 days). CONCLUSION: Our results suggest that adjuvant-induced immunoregulation of donor cells prior to allogeneic cell therapy may augur a new strategy that will bring the benefits of safe cellular immunotherapy aiming to eradicate malignant and nonmalignant pathological cells while avoiding or minimizing the risk of GVHD. 相似文献
1000.
Stiebel-Kalish H Reich E Rainy N Vatine G Nisgav Y Tovar A Gothilf Y Bach M 《European journal of human genetics : EJHG》2012,20(8):884-889
Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative to rodents, including their excellent color vision, precocious retinal development, robust visual testing strategies, low cost, relatively easy transgenesis and shortened experimental times. In this study we will demonstrate the feasibility of using gene-targeting in the zebrafish as a model for the photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA-orthologous cDNA was identified and isolated by PCR amplification. Its expression pattern was determined by whole-mount in-situ hybridization and its function was studied by gene knockdown using two different morpholino-modified oligos (MO), one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f. Visual function was assessed with an optomotor assay on 6-days-post-fertilization larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted in significantly lower vision as measured by the optomotor response compared with uninjected and control MO-injected zebrafish larvae. Histological changes in the Gucy2f-knockdown larvae included loss and shortening of cone and rod outer segments. A zebrafish model of Gucy2f-related LCA1 displays early visual dysfunction and photoreceptor layer dystrophy. This study serves as proof of concept for the use of zebrafish as a simple, inexpensive model with excellent vision on which further study of LCA-related genes is possible. 相似文献