全文获取类型
收费全文 | 124714篇 |
免费 | 8250篇 |
国内免费 | 454篇 |
专业分类
耳鼻咽喉 | 1630篇 |
儿科学 | 3296篇 |
妇产科学 | 2073篇 |
基础医学 | 15962篇 |
口腔科学 | 2370篇 |
临床医学 | 12546篇 |
内科学 | 26374篇 |
皮肤病学 | 1915篇 |
神经病学 | 11963篇 |
特种医学 | 4271篇 |
外国民族医学 | 4篇 |
外科学 | 18132篇 |
综合类 | 1890篇 |
现状与发展 | 1篇 |
一般理论 | 167篇 |
预防医学 | 11112篇 |
眼科学 | 2913篇 |
药学 | 8698篇 |
2篇 | |
中国医学 | 172篇 |
肿瘤学 | 7927篇 |
出版年
2023年 | 511篇 |
2022年 | 831篇 |
2021年 | 2071篇 |
2020年 | 1227篇 |
2019年 | 2013篇 |
2018年 | 2319篇 |
2017年 | 1786篇 |
2016年 | 1961篇 |
2015年 | 2415篇 |
2014年 | 3442篇 |
2013年 | 5333篇 |
2012年 | 7769篇 |
2011年 | 8291篇 |
2010年 | 4689篇 |
2009年 | 4515篇 |
2008年 | 7969篇 |
2007年 | 8520篇 |
2006年 | 8355篇 |
2005年 | 8638篇 |
2004年 | 8169篇 |
2003年 | 8004篇 |
2002年 | 7578篇 |
2001年 | 1194篇 |
2000年 | 940篇 |
1999年 | 1243篇 |
1998年 | 1705篇 |
1997年 | 1426篇 |
1996年 | 1172篇 |
1995年 | 1153篇 |
1994年 | 946篇 |
1993年 | 964篇 |
1992年 | 758篇 |
1991年 | 708篇 |
1990年 | 672篇 |
1989年 | 626篇 |
1988年 | 576篇 |
1987年 | 546篇 |
1986年 | 547篇 |
1985年 | 664篇 |
1984年 | 832篇 |
1983年 | 830篇 |
1982年 | 1162篇 |
1981年 | 1052篇 |
1980年 | 950篇 |
1979年 | 464篇 |
1978年 | 575篇 |
1977年 | 547篇 |
1976年 | 449篇 |
1975年 | 408篇 |
1974年 | 365篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Central nervous system hemangioblastomas, endolymphatic sac tumors, and von Hippel-Lindau disease 总被引:4,自引:0,他引:4
Von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome caused by germline mutations of the VHL tumor suppressor gene.
Major progress has been made in the last decade in both clinical and fundamental aspects of VHL. The VHL gene product, pVHL,
has major and multiple functions: pVHL regulates not only first angiogenesis but also extracellular matrix formation and the
cell cycle. A molecular diagnosis of VHL is now available, leading to a transformation in clinical management of patients
and their families. Diagnosis of VHL has to be suspected in patients with a VHL-related tumor without familial history and
especially in case of hemangioblastoma or endolymphatic sac tumors. Such patients should be systematically investigated for
clinical and molecular evidence of VHL disease. Treatment of symptomatic hemangioblastomas remains mainly neurosurgical, often
in emergency, but stereotactic radiosurgery is emerging as an alternative therapeutic procedure. In the future, antiangiogenic
drugs could represent a potential medical treatment of CNS hemangioblastomas in view of their highly vascular structure. Lastly,
visceral manifestations of VHL disease are also of critical importance and require early detection for effective treatment.
Received: 22 January 2000 / Accepted: 21 February 2000 相似文献
992.
目的 观察并建立不同浓度卡铂损害成年灰鼠前庭终器的离体实验模型。方法 应用前庭终器分离取材技术、前庭器官离体培养技术和组织学检查技术,观察不同浓度卡铂对成年灰鼠前庭各终器的损害。结果 卡铂主要损害灰鼠前庭I型毛细胞,这种损害随着卡铂剂量的增加而加重。结论 卡铂选择性破坏离体培养的灰鼠前庭I型毛细胞。 相似文献
993.
994.
Donglu Zhang Marc Ogan Richard Gedamke Vikram Roongta Renke Dai Mingshe Zhu J Kent Rinehart Lewis Klunk James Mitroka 《Drug metabolism and disposition》2003,31(7):837-845
(3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K channels and has potential to prevent and treat ischemic stroke. Following single intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was extractable from plasma with organic solvents. The unextractable radioactivity remained associated with the proteins (mostly albumin) after SDS-polyacrylamide gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at 110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS-204352, one major radioactive product was isolated and identified as a lysine-adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass spectrometry and NMR analyses as well as by comparison with the synthetic analog, lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS-204352 results from the displacement of the ring-fluorine atom of des-O-methyl BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal incubations of [14C]BMS-204352 resulted in low levels of covalent binding of radioactivity to proteins. This in vitro covalent binding required cytochrome P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A inhibitors ketoconazole and troleadomycin selectively prevented the covalent binding in vitro. Based on these observations, a two-step bioactivation process for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated O-demethylation leading to spontaneous release of HF and the formation of an ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro des-O-methyl BMS-204352 lysine adduct. 相似文献
995.
Yves Claustre Danielle De Peretti Philippe Brun Christiane Gueudet Nathalie Allouard Richard Alonso Jo?lle Lourdelet André Oblin Gabrielle Damoiseau Dominique Fran?on Marie-Fran?oise Suaud-Chagny Régis Steinberg Mireille Sevrin Hans Schoemaker Pascal George Philippe Soubrié Bernard Scatton 《Neuropsychopharmacology》2003,28(12):2064-2076
SSR181507 ((3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT(1A) receptors (K(I)=0.8, 0.2, and 0.2 nM for human D(2), D(3), and 5-HT(1A), respectively). In vivo, SSR181507 inhibited [(3)H]raclopride binding to D(2) receptors in the rat (ID(50)=0.9 and 1 mg/kg, i.p. in limbic system and striatum, respectively). It displayed D(2) antagonist and 5-HT(1A) agonist properties in the same concentration range in vitro (IC(50)=5.3 nM and EC(50)=2.3 nM, respectively, in the GTPgammaS model) and in the same dose range in vivo (ED(50)=1.6 and 0.7 mg/kg, i.p. on striatal DA and 5-HT synthesis, respectively, and 0.03-0.3 mg/kg, i.v. on dorsal raphe nucleus firing rate). It selectively enhanced Fos immunoreactivity in mesocorticolimbic areas as compared to the striatum. This regional selectivity was confirmed in electrophysiological studies where SSR181507, given acutely (0.1-3 mg/kg, i.p.) or chronically (3 mg/kg, i.p., o.d., 22 days), increased or decreased, respectively, the number of spontaneous active DA cells in the ventral tegmental area, but not in the substantia nigra. Moreover, SSR181507 increased both basal and phasic DA efflux (as assessed by microdialysis and electrochemistry) in the medial prefrontal cortex and nucleus accumbens, but not in the striatum. This study shows that the combination of D(2) receptor antagonism and 5-HT(1A) agonism, in the same dose range, confers on SSR181507 a unique neurochemical and electrophysiological profile and suggests the potential of this compound for the treatment of the main dimensions of schizophrenia. 相似文献
996.
We attempt to demonstrate that physicians overdiagnose loxoscelism (colloquially known as 'brown recluse spider bites') by comparing the numbers of such diagnoses to the historically known numbers of Loxosceles spiders from the same areas in four western American states. The medical community from non-endemic Loxosceles areas often makes loxoscelism diagnoses solely on the basis of dermonecrotic lesions where Loxosceles spiders are rare or non-existent. If these diagnoses were correct then Loxosceles populations should be evident, specimens should readily be collected over the years and there should be a reasonable correlation between diagnoses and spider specimens. In 41 months of data collection, we were informed of 216 loxoscelism diagnoses from California, Oregon, Washington and Colorado. In contrast, from these four states, we can only find historical evidence of 35 brown recluse or Mediterranean recluse spiders. There is no consistency between localities of known Loxosceles populations and loxoscelism diagnoses. There are many conditions of diverse etiology that manifest in dermonecrosis. In the western United States, physician familiarity with these conditions will lead to more accurate diagnoses and subsequent proper remedy. 相似文献
997.
998.
Edward L Mattiuz G Douglas Ponsler Robert J Barbuch Paul G Wood John H Mullen Richard L Shugert Qimin Li William J Wheeler Fengjiun Kuo Preston C Conrad John-Michael Sauer 《Drug metabolism and disposition》2003,31(1):88-97
These studies were designed to characterize the disposition and metabolism of atomoxetine hydrochloride [(-)-N-methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride; formerly know as tomoxetine hydrochloride] in Fischer 344 rats and beagle dogs. Atomoxetine was well absorbed from the gastrointestinal tract and cleared primarily by metabolism with the majority of its metabolites being excreted into the urine, 66% of the total dose in the rat and 48% in the dog. Fecal excretion, 32% of the total dose in the rat and 42% in the dog, appears to be due to biliary elimination and not due to unabsorbed dose. Nearly the entire dose was excreted within 24 h in both species. In the rat, low oral bioavailability was observed (F = 4%) compared with the high oral bioavailability in dog (F = 74%). These differences appear to be almost purely mediated by the efficient first-pass hepatic clearance of atomoxetine in rat. The biotransformation of atomoxetine was similar in the rat and dog, undergoing aromatic ring hydroxylation, benzylic oxidation (rat only), and N-demethylation. The primary oxidative metabolite of atomoxetine was 4-hydroxyatomoxetine, which was subsequently conjugated forming O-glucuronide and O-sulfate (dog only) metabolites. Although subtle differences were observed in the excretion and biotransformation of atomoxetine in rats and dogs, the primary difference observed between these species was the extent of first-pass metabolism and the degree of systemic exposure to atomoxetine and its metabolites. 相似文献
999.
BmK 11(2) is a 7216Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch. Nanomolar concentrations of the toxin prolong amphibian nerve action potentials without attenuation of the amplitude. The pharmacological action of the toxin and its sequence similarity to other alpha-scorpion toxins suggest that BmK 11(2) selectively alters voltage-gated Na channels. In order to test whether BmK 11(2) preferentially modulates the gating or kinetics of certain channel isoforms, we applied BmK 11(2) to muscle, heart and neuronal Na channels. 100nM BmK 11(2) increased the peak current amplitude of skeletal muscle (micro1) and neuronal (N1E-115) Na currents by 40 and 20%, respectively, and reduced the cardiac Na (hH1) current by 15%. The toxin slowed current decay of all isoforms, most prominently in N1E-115 (tau(BmK)/tau(Control)=12), micro1 (11), and less so for hH1 (1.3). BmK 11(2) shifted the voltage dependence of activation of micro1 and N1E-115 currents. BmK 11(2) had no effect on steady-state inactivation, use-dependent availability, and the kinetics of entry into slowly recovering inactivated states. 相似文献
1000.