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排序方式: 共有429条查询结果,搜索用时 31 毫秒
41.
Byung Yoon Choi Andrew K. Stewart Anne C. Madeo Shannon P. Pryor Suzanne Lenhard Rick Kittles David Eisenman H. Jeffrey Kim John Niparko James Thomsen Kathleen S. Arnos Walter E. Nance Kelly A. King Christopher K. Zalewski Carmen C. Brewer Thomas Shawker James C. Reynolds John A. Butman Lawrence P. Karniski Seth L. Alper Andrew J. Griffith 《Human mutation》2009,30(4):599-608
Hearing loss with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene encoding pendrin, a transmembrane Cl?/I?/HCO exchanger. Pendrin's critical transport substrates are thought to be I? in the thyroid gland and HCO in the inner ear. We previously reported that bi‐allelic SLC26A4 mutations are associated with Pendred syndromic EVA whereas one or zero mutant alleles are associated with nonsyndromic EVA. One study proposed a correlation of nonsyndromic EVA with SLC26A4 alleles encoding pendrin with residual transport activity. Here we describe the phenotypes and SLC26A4 genotypes of 47 EVA patients ascertained since our first report of 39 patients. We sought to determine the pathogenic potential of each variant in our full cohort of 86 patients. We evaluated the trafficking of 11 missense pendrin products expressed in COS‐7 cells. Products that targeted to the plasma membrane were expressed in Xenopus oocytes for measurement of anion exchange activity. p.F335L, p.C565Y, p.L597S, p.M775T, and p.R776C had Cl?/I? and Cl?/HCO exchange rate constants that ranged from 13 to 93% of wild type values. p.F335L, p.L597S, p.M775T and p.R776C are typically found as mono‐allelic variants in nonsyndromic EVA. The high normal control carrier rate for p.L597S indicates it is a coincidentally detected nonpathogenic variant in this context. We observed moderate differential effects of hypo‐functional variants upon exchange of HCO versus I? but their magnitude does not support a causal association with nonsyndromic EVA. However, these alleles could be pathogenic in trans configuration with a mutant allele in Pendred syndrome. Hum Mutat 0, 1–10, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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43.
Cylwik B Chrostek L Zalewski B Dabrowski A Szmitkowski M 《Digestive diseases and sciences》2007,52(9):2317-2322
The purpose of this study was to evaluate the usefulness of serum total sialic acid (SA) for discrimination of malignant and
nonmalignant jaundice. Serum SA concentration and its ratio with total protein (SA/TP) were determined in 55 patients with
jaundice: 25 malignant and 30 nonmalignant. SA was estimated by enzymatic method. Serum total SA and the ratio SA/TP were
significantly higher in malignant than in nonmalignant jaundice. Diagnostic sensitivity of SA and the ratio of SA/TP in both
types of jaundice reached the value of 95.8%. The specificity, positive and negative predictive values, and efficiency of
SA and SA/TP were higher in malignant than in nonmalignant jaundice. Areas under ROC curves for SA and the ratio of SA/TP
in malignant jaundice were higher than in nonmalignant, but there were not statistically significant differences. SA levels
and the ratio of SA/TP do not have the ability to discriminate between these types of jaundice. 相似文献
44.
M. Giannetti H. A. Schroeder A. Zalewski N. Gonsalves P. J. Bryce 《Diseases of the esophagus》2015,28(8):705-710
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized pathologically by eosinophil infiltration. In addition to loss of barrier integrity, a dominant T Helper 2‐associated immune response and strong allergic connection, the esophagus tissue undergoes dramatic changes, with frequent presence of mucosal rings, strictures, linear furrows, and trachealization. Although the inflammatory mechanisms behind this disease are being increasingly well understood, the structural features remain unexplained. We examined the expression of key members of the Wnt‐signaling pathway in biopsies from patients with EoE. This pathway has been shown to be critically important in regulating cellular homeostasis, growth, and differentiation and to be dysregulated in several disease conditions. Biopsies from adult EoE patients were collected by endoscopy and mRNA extracted. After cDNA synthesis, the relative gene expression from key upstream (secreted frizzled‐related protein 1) and downstream (c‐myc and Cyclin D1) molecules in the Wnt pathway, as well as several Wnt pathway members (Wnt1, Axin1, low‐density lipoprotein receptor‐related protein 6, glycogen synthase kinase 3 beta, and β‐catenin), were determined. Biopsies from patients with EoE displayed significantly higher expression of secreted frizzed‐related protein 1 than controls, as well as reductions in Cyclin D1 and c‐myc. In contrast, there were no differences in the Wnt pathway molecules. The levels of expression of Cyclin D1 and c‐myc, as well as β‐catenin, in EoE patients showed strong correlations with the frequency of esophageal eosinophils. Our findings suggest that although there are no changes in the overall levels of key Wnt pathway genes in adult EoE, there is evidence for dysregulation of upstream and downstream regulators of Wnt signaling. Importantly, the associations with eosinophilia suggest that these may participate in the pathogenesis of this disease and be markers of disease severity. 相似文献
45.
46.
Maureen Zalewski Sherryl H. Goodman Pamela M. Cole Katie A. McLaughlin 《Clinical psychology》2017,24(4):370-388
When providing mental health services to adults, we are often treating individuals who, among their other roles, are also parents. The goal of this article was to provide practitioners with the state of the science about both the impact of parental psychopathology on children and the role that children's well‐being has in parental psychopathology. We discuss the benefits of integrated care for adult clients who are parents, as well as the barriers to providing integrated care for both parents and children in psychotherapy, and provide recommendations for practice. With this information, practitioners will gain greater awareness of their opportunities to treat adults in their parenting roles as well as to contribute to prevention of mental disorders in children. 相似文献
47.
48.
Evidence for reduced fibrinolytic activity in unstable angina at rest. Clinical, biochemical, and angiographic correlates 总被引:17,自引:0,他引:17
A Zalewski Y Shi D Nardone B Bravette P Weinstock D Fischman P Wilson S Goldberg D C Levin T D Bjornsson 《Circulation》1991,83(5):1685-1691
BACKGROUND. The goal of this study was to evaluate the role of the fibrinolytic system in patients with unstable angina at rest associated with transient electrocardiographic changes. METHODS AND RESULTS. Tissue plasminogen activator activity in plasma was comparable among patients with unstable angina (n = 17), patients with stable exertional angina (n = 10), and control patients with normal coronary arteriograms (n = 8). In contrast, plasminogen activator inhibitor-1 (PAI-1) activity in plasma was elevated in the unstable angina group (21.67 +/- 9.52 AU/ml) as compared with either the stable angina group (12.01 +/- 7.06 AU/ml, p less than 0.02) or the controls (12.49 +/- 8.54 AU/ml, p less than 0.02). Coronary angiography performed within 24 hours after the last anginal episode showed a similar extent of coronary artery disease in the unstable and stable angina groups. However, intracoronary thrombi were observed in eight patients in the unstable angina group while no thrombus was noted in the stable angina group (chi 2 = 7.22, p less than 0.01). CONCLUSIONS. We conclude that patients with unstable angina at rest have a reduced fibrinolytic activity and an increased incidence of intracoronary thrombi. It is postulated that elevated PAI-1 activity in the presence of coronary arterial wall injury may be an important factor leading to the development of acute coronary syndromes. 相似文献
49.
Shi Y Niculescu R Wang D Patel S Davenpeck KL Zalewski A 《Arteriosclerosis, thrombosis, and vascular biology》2001,21(5):739-745
Reactive oxygen species (ROS), produced by cellular constituents of the arterial wall, provide a signaling mechanism involved in vascular remodeling. Because adventitial fibroblasts are actively involved in coronary remodeling, we examined whether the changes in the redox state affect their phenotypic characteristics. To this end, superoxide anion production and NAD(P)H oxidase activity were measured in porcine coronary arteries in vivo, and the effect of ROS generation on adventitial fibroblast proliferation was examined in vitro. Superoxide production (SOD- and Tiron-inhibitable nitro blue tetrazolium [NBT] reduction) increased significantly within 24 hours after balloon-induced injury, with the product of NBT reduction present predominantly in adventitial fibroblasts. These changes were NAD(P)H oxidase-dependent, because diphenyleneiodonium (DPI) abolished superoxide generation (P<0.001). Furthermore, the injury-induced superoxide production was associated with augmented NAD(P)H oxidase activity and upregulation of p47(phox) and p67(phox) in adventitial fibroblasts (immunohistochemistry). Serum stimulation of isolated adventitial fibroblasts produced time-dependent increases in ROS production (peak 3 to 6 hours). The inhibition of ROS generation with NAD(P)H oxidase inhibitor (DPI) or the removal of ROS with antioxidants (Tiron, catalase) abrogated proliferation of adventitial fibroblasts. These results indicate that vascular NAD(P)H oxidase plays a central role in the upregulation of oxidative stress after coronary injury, providing pivotal growth signals for coronary fibroblasts. 相似文献
50.
Effective therapy for patients with unstable angina or evolving myocardial infarction following coronary bypass surgery requires accurate delineation of the pathoanatomy and prompt intervention. We therefore performed cardiac catheterization in 10 consecutive patients: four with acute myocardial infarction and six with refractory unstable angina (NYHA class IV). All patients with acute myocardial infarction were found to have completely thrombosed vein grafts supplying totally occluded native coronary arteries. In three patients with evolving myocardial infarction occurring within 4 weeks of coronary bypass surgery, graft thrombosis was caused by venous valves in two patients and a suboptimal anastomosis in a third. The fourth patient sustained a myocardial infarction 7 years after coronary bypass surgery with atherosclerotic plaque rupture causing vein graft thrombosis. Therapy with intragraft streptokinase resulted in complete clearing of thrombus, pain relief, and control of injury current in all four patients. Rest angina with concomitant ST and T wave changes occurred in six patients. In two patients symptoms occurred early (within 6 months), whereas angina developed 4 to 10 years after coronary bypass graft surgery in four patients. In the two patients with early recurrence of symptoms suboptimal anastomosis was found in one, while the other patient had a venous valve in the vein graft in conjunction with a stenosis in the native coronary artery. In three of four patients with late recurrence of angina, symptoms developed as a result of atherosclerotic stenosis in their vein grafts; in the fourth patient an occluded graft was found to supply a stenosed native coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献