全文获取类型
收费全文 | 489篇 |
免费 | 36篇 |
国内免费 | 27篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 20篇 |
妇产科学 | 3篇 |
基础医学 | 69篇 |
口腔科学 | 19篇 |
临床医学 | 77篇 |
内科学 | 184篇 |
皮肤病学 | 8篇 |
神经病学 | 13篇 |
特种医学 | 26篇 |
外科学 | 38篇 |
综合类 | 18篇 |
预防医学 | 15篇 |
药学 | 26篇 |
中国医学 | 1篇 |
肿瘤学 | 32篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 10篇 |
2016年 | 8篇 |
2015年 | 9篇 |
2014年 | 8篇 |
2013年 | 15篇 |
2012年 | 11篇 |
2011年 | 12篇 |
2010年 | 17篇 |
2009年 | 20篇 |
2008年 | 16篇 |
2007年 | 21篇 |
2006年 | 28篇 |
2005年 | 35篇 |
2004年 | 16篇 |
2003年 | 18篇 |
2002年 | 32篇 |
2001年 | 31篇 |
2000年 | 23篇 |
1999年 | 21篇 |
1998年 | 25篇 |
1997年 | 26篇 |
1996年 | 19篇 |
1995年 | 14篇 |
1994年 | 16篇 |
1993年 | 5篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 4篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1971年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有552条查询结果,搜索用时 15 毫秒
1.
2.
F Reichenberger R Voswinckel B Enke M Rutsch E El Fechtali T Schmehl H Olschewski R Schermuly N Weissmann H A Ghofrani F Grimminger E Mayer W Seeger 《The European respiratory journal》2007,30(5):922-927
For chronic thromboembolic pulmonary hypertension not amenable to pulmonary endarterectomy, effective medical therapy is desired. In an open-label uncontrolled clinical trial, 104 patients (mean +/- sem age 62 +/- 11 yrs) with inoperable chronic thromboembolic pulmonary hypertension were treated with 50 mg sildenafil t.i.d. At baseline, patients had severe pulmonary hypertension (pulmonary vascular resistance 863 +/- 38 dyn.s.cm(-5)) and a 6-min walking distance of 310 +/- 11 m. Eight patients were in World Health Organization functional class II, 76 in class III and 20 in class IV. After 3 months' treatment, there was significant haemodynamic improvement, with reduction of pulmonary vascular resistance to 759 +/- 62 dyn.s.cm(-5). The 6-min walking distance increased significantly to 361 +/- 15 m after 3 months' treatment, and to 366 +/- 18 m after 12 months' treatment. A subset of 67 patients received a single dose of 50 mg sildenafil during initial right heart catheterisation. The acute haemodynamic effect of this was not predictive of long-term outcome. In this large series of patients with inoperable chronic thromboembolic pulmonary hypertension, open-label treatment with sildenafil led to significant long-term functional improvement. The acute effect of sildenafil may not predict the long-term outcome of therapy. 相似文献
3.
The influence of exogenously supplied free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the 5-lipoxygenase metabolism in human neutrophils (PMN) was investigated. Simultaneous application of A23187 with incremental concentrations of free AA caused a dose-dependent augmentation of the ionophore-elicited eicosanoid generation [release of leukotriene B4 and its omega-oxidation products, nonenzymatic hydrolysis products of leukotriene A4, and 5-hydroxyeicosatetraeneoic acid (5-HETE)]. A23187 challenge in the presence of free EPA resulted in the dose-dependent appearance of corresponding n - 3-derived metabolites, parallelled by a decrease in 4-series leukotrienes and 5-HETE. The inflammatory ligands formyl-methionyl-leucyl-phenylalanine and platelet-activating factor evoked no substantial eicosanoid generation in the absence of exogenously supplied polyunsaturated fatty acids (PUFAs). Addition of free AA or EPA in parallel with the ligand challenge evoked exclusive and dose-dependent generation of the respective leukotrienes and 5-HETE or 5-hydroxyeicosapentaenoic acid. Total amounts of 5-lipoxygenase products elicited under these conditions approached those in ionophore-stimulated PMN, with platelet-activating factor challenge surpassing the formyl-methionyl-leucylphenylalanine-evoked effect by approximately 50%. Two thirds of the maximum effect was obtained in the presence of only 10 microM free PUFA. Use of labeled fatty acids suggested exclusive origin of the eicosanoids from the exogenously provided precursor PUFA. Critical dependence on timing was noted; maximum response occurred upon simultaneous application of PUFA and ligand, and only 5 min of delay between AA or EPA addition and ligand challenge sufficed to reduce the formation of respective metabolites to less than 20%. EPA competed with AA and was noted to be the preferred substrate for ligand-evoked eicosanoid synthesis. In contrast to the simultaneous addition of free PUFAs, preloading of PMN with AA or EPA for 60 min revealed only very moderate or even no influence on ionophore- or ligand-evoked eicosanoid synthesis. We conclude that inflammatory ligands induce marked stimulation of PMN eicosanoid synthesis, with critical dependence on the presence of free precursor PUFAs. Preference of EPA over AA is observed under these conditions. 相似文献
4.
5.
6.
doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH) 总被引:12,自引:0,他引:12
des Portes V; Francis F; Pinard JM; Desguerre I; Moutard ML; Snoeck I; Meiners LC; Capron F; Cusmai R; Ricci S; Motte J; Echenne B; Ponsot G; Dulac O; Chelly J; Beldjord C 《Human molecular genetics》1998,7(7):1063-1070
Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical
dysgenesis disorder associated with a defect in neuronal migration.
Clinical manifestations are epilepsy and mental retardation. This disorder,
which mainly affects females, can be inherited in a single pedigree with
lissencephaly, a more severe disease which affects the male individuals.
This clinical entity has been described as X- SCLH/LIS syndrome. Recently
we have demonstrated that the doublecortin gene, which is localized on the
X chromosome, is implicated in this disorder. We have now performed a
systematic mutation analysis of doublecortin in 11 unrelated females with
SCLH (one familial and 10 sporadic cases) and have identified mutations in
10/11 cases. The sequence differences include nonsense, splice site and
missense mutations and these were found throughout the gene. These results
provide strong evidence that loss of function of doublecortin is the major
cause of SCLH. The absence of phenotype-genotype correlations suggests that
X-inactivation patterns of neuronal precursor cells are likely to
contribute to the variable clinical severity of this disorder in females.
相似文献
7.
8.
Stein TP; Oram-Smith JC; Leskiw MJ; Wallace HW; Long LC; Leonard JM 《The American journal of physiology》1976,230(5):1321-1325
9.
Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA 总被引:2,自引:2,他引:2
Rozmahel R; Gyomorey K; Plyte S; Nguyen V; Wilschanski M; Durie P; Bear CE; Tsui LC 《Human molecular genetics》1997,6(7):1153-1162
We have used a mouse model to study the ability of human CFTR to correct
the defect in mice deficient of the endogenous protein. In this model,
expression of the endogenous Cftr gene was disrupted and replaced with a
human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for
the gene replacement failed to show neither improved intestinal pathology
nor survival when compared to mice completely lacking CFTR. RNA analyses
showed that the human CFTR sequence was transcribed from the targeted
allele in the respiratory and intestinal epithelial cells. Furthermore, in
vivo potential difference measurements showed that basal CFTR chloride
channel activity was present in the apical membranes of both nasal and
rectal epithelial cells in all homozygous knock-in animals examined. Ussing
chamber studies showed, however, that the cAMP-mediated chloride channel
function was impaired in the intestinal tract among the majority of
homozygous knock-in animals. Hence, failure to correct the intestinal
pathology associated with loss of endogenous CFTR was related to
inefficient functional expression of the human protein in mice. These
results emphasize the need to understand the tissue- specific expression
and regulation of CFTR function when animal models are used in gene therapy
studies.
相似文献
10.
L Ermert S Rousseau H Schütte R G Birkemeyer F Grimminger S Bhakdi H R Duncker W Seeger 《Laboratory investigation; a journal of technical methods and pathology》1992,66(3):362-369
S. aureus alpha-toxin and E. coli hemolysin (Hly) represent two prototypes of pore-forming cytolysins. Both are established virulence factors and have been implicated in the development of septic lung failure. Low doses of these agents cause thromboxane-mediated vasoconstriction and edema formation in isolated perfused rabbit lungs. In a preceding investigation, we observed that alpha-toxin causes overt endothelial cell damage in these lungs, as demonstrable by electron microscopy (Seeger W, Birkemeyer RG, Ermert L, Suttorp N, Bhakdi S, Duncker HR: Lab Invest 63:341, 1990). Here, we present results of a parallel study conducted with E. coli hemolysin. Thromboxane-dependent pulmonary hypertension was suppressed by the addition of acetylsalicylic acid to the perfusion fluid in all cases. Administration of 0.2 hemolytic units (HU; i.e., 20 ng/ml protein) resulted in progressive weight gain after a lag period of 10 to 15 minutes, and 30 minutes after toxin application the gravimetrically determined capillary filtration coefficients (Kfc) were increased greater than 10-fold. Perfusion was terminated when the total lung weight gain surpassed 20 gm. 0.12 HU/ml E. coli hemolysin caused 2- to 3-fold increased capillary filtration coefficients values within 110 minutes, concomitant with intermediate quantities of edema formation (9.7 +/- 2.7 gm). Potassium liberation in the absence of lactate dehydrogenase release occurred in all toxin treated lungs. Electron microscopic examination after perfusion fixation revealed interstitial edema formation in areas remote from the blood-gas exchange barrier. Increased numbers of endothelial plasmalemmal vesicles were visualized at the very onset of edema formation in lungs exposed to 0.2 HU/ml, and after a 110-minute exposure to 0.12 HU/ml of the toxin, but not in lungs exhibiting severe edema (greater than 20 gm weight gain). In contrast to our previous results with alpha-toxin, endothelial cells displayed normal electron density here and were not detached from the fused basal lamina. Hence, although both pore formers provoke severe vascular leakage in our experimental model, the underlying pathways probably divert fundamentally from each other. 相似文献