全文获取类型
收费全文 | 509篇 |
免费 | 44篇 |
专业分类
儿科学 | 36篇 |
妇产科学 | 5篇 |
基础医学 | 91篇 |
口腔科学 | 4篇 |
临床医学 | 31篇 |
内科学 | 112篇 |
皮肤病学 | 5篇 |
神经病学 | 41篇 |
特种医学 | 7篇 |
外科学 | 113篇 |
综合类 | 5篇 |
预防医学 | 22篇 |
眼科学 | 11篇 |
药学 | 34篇 |
中国医学 | 3篇 |
肿瘤学 | 33篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 11篇 |
2020年 | 12篇 |
2019年 | 10篇 |
2018年 | 13篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 13篇 |
2014年 | 20篇 |
2013年 | 22篇 |
2012年 | 38篇 |
2011年 | 30篇 |
2010年 | 24篇 |
2009年 | 12篇 |
2008年 | 32篇 |
2007年 | 38篇 |
2006年 | 23篇 |
2005年 | 24篇 |
2004年 | 25篇 |
2003年 | 36篇 |
2002年 | 32篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 12篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 11篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有553条查询结果,搜索用时 15 毫秒
61.
Fritsch T Smyth KA McClendon MJ Ogrocki PK Santillan C Larsen JD Strauss ME 《Journal of the American Geriatrics Society》2005,53(7):1191-1196
OBJECTIVES: To study the associations between dementia/mild cognitive impairment (MCI) and cognitive performance and activity levels in youth. DESIGN: Retrospective cohort study. SETTING: Research volunteers living throughout the United States. PARTICIPANTS: A total of 396 persons (mean age 75) who were graduates of the same high school in the mid-1940s. MEASUREMENTS: Adolescent intelligence quotient (IQ) scores were gathered from archived student records, and activity levels were determined from yearbooks. A two-stage telephone screening procedure (Modified Telephone Interview for Cognitive Status or Informant Questionnaire on Cognitive Decline in the Elderly followed by Dementia Questionnaire) was used to determine adult cognitive status. Data were analyzed using logistic regression to model the risk of cognitive impairment (dementia/MCI) versus no cognitive impairment as a function of IQ and activity level, adjusting for sex and education. RESULTS: High adolescent IQ and greater activity level were each independently associated with a lower risk for dementia/MCI (odds ratio (OR) for a 1-standard deviation increase in IQ=0.51, 95% confidence interval (CI)=0.32-0.79; OR for a unit increase in activity=0.32, 95% CI=0.12-0.84). No association was found between sex or education and adult cognitive status in this model. CONCLUSION: High IQ and greater activity levels in youth reduce the risk for cognitive impairments in aging. The mechanism(s) underlying these associations are unknown, but intelligence may be a marker for cognitive/neurological "reserve," and involvement in activities may contribute to "reserve." Early neuropathology and ascertainment bias are also possible explanations for the observed associations. 相似文献
62.
Na Song Javier J. Concepcion Robert A. Binstead Jennifer A. Rudd Aaron K. Vannucci Christopher J. Dares Michael K. Coggins Thomas J. Meyer 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(16):4935-4940
In aqueous solution above pH 2.4 with 4% (vol/vol) CH3CN, the complex [RuII(bda)(isoq)2] (bda is 2,2′-bipyridine-6,6′-dicarboxylate; isoq is isoquinoline) exists as the open-arm chelate, [RuII(CO2-bpy-CO2−)(isoq)2(NCCH3)], as shown by 1H and 13C-NMR, X-ray crystallography, and pH titrations. Rates of water oxidation with the open-arm chelate are remarkably enhanced by added proton acceptor bases, as measured by cyclic voltammetry (CV). In 1.0 M PO43–, the calculated half-time for water oxidation is ∼7 μs. The key to the rate accelerations with added bases is direct involvement of the buffer base in either atom–proton transfer (APT) or concerted electron–proton transfer (EPT) pathways.Metal-complex catalyzed water oxidation continues to evolve with new catalysts and new mechanistic insights (1–9). Studies on single-site Ru catalysts such as [RuII(Mebimpy)(bpy)(OH2)]2+ [Mebimpy is 2,6-bis(1-methylbenzimidazol-2-yl)pyridine; bpy is 2,2′-bipyridine; Fig. 1], both in solution and on surfaces, reveal mechanisms in which stepwise oxidative activation of aqua precursors to RuV=O is followed by rate-limiting O–O bond formation (10–15). The results of kinetic and mechanistic studies have revealed the importance of concerted atom–proton transfer (APT) in the O–O bond-forming step. In APT, the O–O bond forms in concert with H+ transfer to water or to an added base (11, 12, 16–19). APT can promote dramatic rate enhancements. In a recent study on surface-bound [Ru(Mebimpy)(4,4′-((HO)2OPCH2)2bpy)(OH2)]2+ [4,4′-((HO)2OPCH2)2bpy is 4,4′-bis-methlylenephosphonato-2,2′-bipyridine] stabilized by atomic layer deposition, a rate enhancement of ∼106 was observed with 0.012 M added PO43− at pH 12 compared with oxidation at pH 1 (20).Open in a separate windowFig. 1.Structures of [RuII(Mebimpy)(bpy)(OH2)]2+ (Left) and [RuII(CO2-bpy-CO2)(isoq)2] [1] (Right).Sun and coworkers (21, 22) have described the Ru single-site water oxidation catalysts, [RuII(bda)(L)2] (H2bda is 2,2′-bipyridine-6,6′-dicarboxylic acid, HCO2-bpy-CO2H; L is isoquinoline, 4-picoline, or phthalazine). They undergo rapid and sustained water oxidation catalysis with added CeIV. A mechanism has been proposed in which initial oxidation to seven coordinate RuIV is followed by further oxidation to RuV(O) with O–O coupling to give a peroxo-bridged intermediate, RuIVO–ORuIV, which undergoes further oxidation and release of O2 (21, 22). We report here the results of a rate and mechanistic study on electrochemical water oxidation by complex [1], [RuII(CO2-bpy-CO2)(isoq)2] (isoq is isoquinoline) (Fig. 1). Evidence is presented for water oxidation by a chelate open form in acidic solutions. The chelate open form displays dramatic rate enhancements with added buffer bases, and the results of a detailed mechanistic study are reported here. 相似文献
63.
Axel R. Concepcion January T. Salas Elena Sáez Sarai Sarvide Alex Ferrer Ainhoa Portu Iker Uriarte Sandra Hervás-Stubbs Ronald P.J. Oude Elferink Jesús Prieto Juan F. Medina 《Oncotarget》2015,6(30):28588-28606
Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of unknown etiopathogenesis showing progressive autoimmune-mediated cholangitis. In PBC patients, the liver and lymphocytes exhibit diminished expression of AE2/SLC4A2, a Cl−/HCO3− anion exchanger involved in biliary bicarbonate secretion and intracellular pH regulation. Decreased AE2 expression may be pathogenic as Ae2a,b−/− mice reproduce hepatobiliary and immunological features resembling PBC. To understand the role of AE2 deficiency for autoimmunity predisposition we focused on the phenotypic changes of T cells that occur over the life-span of Ae2a,b−/− mice. At early ages (1-9 months), knockout mice had reduced numbers of intrahepatic T cells, which exhibited increased activation, programmed-cell-death (PD)-1 expression, and apoptosis. Moreover, young knockouts had upregulated PD-1 ligand (PD-L1) on bile-duct cells, and administration of neutralizing anti-PD-L1 antibodies prevented their intrahepatic T-cell deletion. Older (≥10 months) knockouts, however, showed intrahepatic accumulation of cytotoxic CD8+ T cells with downregulated PD-1 and diminished apoptosis. In-vitro DNA demethylation with 5-aza-2′-deoxycytidine partially reverted PD-1 downregulation of intrahepatic CD8+ T cells from aged knockouts. Conclusion: Early in life, AE2 deficiency results in intrahepatic T-cell activation and PD-1/PD-L1 mediated deletion. With aging, intrahepatic CD8+ T cells epigenetically suppress PD-1, and their consequential expansion and further activation favor autoimmune cholangitis. 相似文献
64.
Liver Transplantation for Uncontrollable Variceal Bleeding 总被引:1,自引:0,他引:1
Hiroto Ewaga M.D. Emmet B. Keeffe M.D. F.A.C.G. Jonathan Dort M.D. Waldo Concepcion M.D. Carlos O. Esquivel M.D. Ph.D. 《The American journal of gastroenterology》1994,89(10):1823-1826
Objectives: A small number of liver transplant candidates experience variceal bleeding that cannot be controlled by standard medical therapy. The objective of this study was to analyze the role of urgent liver transplantation for this subset of patients with acute, refractory, portal hypertensive bleeding. Methods: Retrospective review of data from 416 patients undergoing 449 liver transplantations between March, 1988 and February, 1993 revealed seven patients (1.7%) with endstage liver disease who underwent transplantation for uncontrollable variceal bleeding. All patients failed therapy with intravenous pitressin, endoscopic sclerotherapy, balloon tamponade, and/or transjugular intrahepatic portosystemic shunt and continued to bleed. Patients ranged in age from 6 months to 56 years. All patients were Child's class C. Two patients were listed for transplantation with the United Network for Organ Sharing as status 3, and five patients were listed as status 4. Results: All patients underwent successful liver transplantation with immediate control of bleeding. One patient expired on the 26th postoperative day from multiple organ failure, and another patient expired with recurrent hep-atocellular carcinoma on the 110th postoperative day. No patients experienced late rebleeding from varices after transplantation. Conclusions: Urgent liver transplantation is effective and feasible for the small subset of patients with uncontrollable variceal bleeding and endstage liver disease. Prompt and complete evaluation of the potential recipient and availability of a donor organ are critical to the success of this approach. 相似文献
65.
Joanna M.M. Howson Jason D. Cooper Deborah J. Smyth Neil M. Walker Helen Stevens Jin-Xiong She George S. Eisenbarth Marian Rewers John A. Todd Beena Akolkar Patrick Concannon Henry A. Erlich Cécile Julier Grant Morahan J?rn Nerup Concepcion Nierras Flemming Pociot Stephen S. Rich and the Type Diabetes Genetics Consortium 《Diabetes》2012,61(11):3012-3017
The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10−6 and 2.5 × 10−5, respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/2q33.2 was obtained (P = 7.90 × 10−5). No evidence of differential risk by sex was obtained at any loci (P ≥ 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease.Knowledge of the genetic architecture of type 1 diabetes has increased recently owing to large-scale genome-wide association (GWA) studies (1–3). Estimates of the contributions of the HLA region and numerous non-HLA loci across the genome now account for a sizeable proportion of familial clustering of the disorder (4–6). However, there remains substantial familial clustering that is not explained by the known loci (likely to be in excess of 40%) (4–6). Interactions between risk loci beyond that of a multiplicative model on the odds ratio (OR) scale (or additive on the log odds scale (7)) could account for some of the “missing heritability.” In addition, the existence of differential effects according to age-at-diagnosis and sex remains relatively unexplored.The HLA region on chromosome 6p21 is the major source of familial clustering in type 1 diabetes (4). HLA-DRB1 and HLA-DQB1 are associated with ORs in excess of 10 for susceptible genotypes (or less than 0.1 for protective genotypes) (8). The risk genotype HLA-DRB1*03/HLA-DRB1*04-HLA-DQB1*0302 (referred to as DR3/DR4-DQ302) with greatest effect has been shown to have the highest frequency in the individuals with youngest onset (9). An age-at-diagnosis interaction has also been reported for HLA-DRB1*04 (10) and the HLA class I alleles HLA-A*24 and HLA-B*39 (11,12).In contrast, reports of age-at-diagnosis interaction effects at non-HLA loci are contradictory, with positive reports largely confined to studies involving small sample sets (3,13–15). Similarly, reports of gene–gene interaction of type 1 diabetes–associated regions are also mainly conflicting (16–19), we presume due to inadequate sample sizes, with most positive reports likely to be false because the false-discovery rate would be high in these underpowered studies. The only convincing gene–gene interaction reported, is between a major non-HLA locus, protein tyrosine phosphatase nonreceptor type 22 (PTPN22) and DR3/DR4-DQ302 genotypes (20–23).The incidence of childhood type 1 diabetes is similar in males and females, unlike other autoimmune diseases such as Graves disease, celiac disease, or multiple sclerosis. Despite similar frequencies of childhood type 1 diabetes by sex, there have been reports of genetic risk factors differing between males and females (22,24).Given that most studies of gene–gene interaction, age-at-diagnosis effects, and sex effects on type 1 diabetes risk have not been addressed in sufficiently well-powered studies, the Type 1 Diabetes Genetics Consortium (T1DGC) has collected more than 16,000 type 1 diabetes–affected samples and tested them for interaction effects with sex and age-at-diagnosis at 38 non-HLA type 1 diabetes–associated regions (Supplementary Table 2). Gene–gene interaction was also tested between HLA class II and the 38 non-HLA loci. With this very large sample set, the study had at least 80% power to detect effects as small as an interaction OR = 1.12 for sex and 1.19 for interactions with age-at-diagnosis or HLA. These calculations assume a multiplicative (log additive) effects model, an OR = 1.15 for association with type 1 diabetes for the test locus and a minor allele frequency of 0.2 and α = 0.0004. In contrast, with 5,000 samples, which is twice as large as any other study testing for interaction effects in type 1 diabetes published to date, the study would only be powered at 80% to detect interaction effects larger than an OR = 1.3 with sex (with the same assumptions as above). For age-at-diagnosis interaction, an OR ≥ 1.37 could be detected; for HLA interaction, an OR ≥ 1.38 could be detected (Supplementary Figs. 1–6). 相似文献
66.
David J. Stewart Javier J. Concepcion M. Kyle Brennaman Robert A. Binstead Thomas J. Meyer 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(3):876-880
Visible light excitation of the ligand-bridged assembly [(bpy)2RuaII(L)RubII(bpy)(OH2)4+] (bpy is 2,2′-bipyridine; L is the bridging ligand, 4-phen-tpy) results in emission from the lowest energy, bridge-based metal-to-ligand charge transfer excited state (L−•)RubIII-OH2 with an excited-state lifetime of 13 ± 1 ns. Near–diffusion-controlled quenching of the emission occurs with added HPO42− and partial quenching by added acetate anion (OAc−) in buffered solutions with pH control. A Stern–Volmer analysis of quenching by OAc− gave a quenching rate constant of kq = 4.1 × 108 M−1⋅s−1 and an estimated pKa* value of ∼5 ± 1 for the [(bpy)2RuaII(L•−)RubIII(bpy)(OH2)4+]* excited state. Following proton loss and rapid excited-state decay to give [(bpy)2RuaII(L)RubII(bpy)(OH)3+] in a H2PO4−/HPO42− buffer, back proton transfer occurs from H2PO4− to give [(bpy)2RuaII(L)Rub(bpy)(OH2)4+] with kPT,2 = 4.4 × 108 M−1⋅s−1. From the intercept of a plot of kobs vs. [H2PO4−], k = 2.1 × 106 s−1 for reprotonation by water providing a dramatic illustration of kinetically limiting, slow proton transfer for acids and bases with pKa values intermediate between pKa(H3O+) = −1.74 and pKa(H2O) = 15.7. 相似文献
67.
Dixon B. Kaufman George W. Burke III David S. Bruce Christopher P. Johnson A. Osama Gaber David E. R. Sutherland Robert M. Merion Scott A. Gruber Eugene Schweitzer John P. Leone Christopher L. Marsh Edward Alfrey Waldo Concepcion Mark D. Stegall James A. Schulak Paul F. Gores Enrico Benedetti Craig Smith Alice K. Henning Fernando Kuehnel Sarah King William E. Fitzsimmons 《American journal of transplantation》2003,3(7):855-864
A randomized, multicenter, prospective study was conducted at 18 pancreas transplant centers in the United States to determine the role of induction therapy in simultaneous pancreas-kidney (SPK) transplantation. One hundred and 74 recipients were enrolled: 87 recipients each in the induction and noninduction treatment arms. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and corticosteroids. There were no statistically significant differences between treatment groups for patient, kidney, and pancreas graft survival at 1-year. The 1-year cumulative incidence of any treated biopsy-confirmed or presumptive rejection episodes (kidney or pancreas) in the induction and noninduction treatment arms was 24.6% and 31.2% (p = 0.28), respectively. The 1-year cumulative incidence of biopsy-confirmed, treated, acute kidney allograft rejection in the induction and noninduction treatment arms was 13.1% and 23.0% (p = 0.08), respectively. Biopsy-confirmed kidney allograft rejection occurred later post-transplant and appeared to be less severe among recipients that received induction therapy. The highest rate of Cytomegalovirus (CMV) viremia/syndrome was observed in the subgroup of recipients who received T-cell depleting antibody induction and received organs from CMV serologically positive donors. Decisions regarding the routine use of induction therapy in SPK transplantation must take into consideration its differential effects on risk of rejection and infection. 相似文献
68.
Enrique Soto-Pedre Maria Concepcion Hernaez-Ortega Jose Antonio Vazquez 《Ophthalmic epidemiology》2013,20(5):335-341
Objective: To identify the potential risk factors for postvitrectomy diabetic vitreous hemorrhage (PDVH). Methods: A matched case-control nested into a retrospective follow-up study was done to review the surgical results in 68 consecutive eyes undergoing primary pars plana vitrectomy for vitreous hemorrhage. The eyes were divided into two groups based on the presence of PDVH (19 cases and 49 controls) and were matched on surgeon and the date of surgery. Twenty-three factors related to the preoperative examination and eight factors related to the operative procedure were analyzed. Statistical analysis was based on conditional logistic regression models with PDVH as the dependent variable. The mean follow-up interval was six months. Results: The factors associated with the incidence of PDVH were iris neovascularization (OR = 9.8, P = 0.03), lower extremity amputations (OR = 8.3, P = 0.02) and the use of antihypertensive agents within three months before vitrectomy (OR = 0.2, P = 0.04). Phakic and aphakic eyes of diabetic patients with lower extremity amputations would have a 70% probability of developing PDVH. This probability would have dropped to 30–40% had they been taking antihypertensive treatment. Conclusions: Iris neovascularization and lower extremity amputations increase the risk of PDVH. Antihypertensive treatment before vitrectomy decreases this risk. 相似文献
69.
70.
L Bailey W Concepcion H Shattuck L Huang 《The Journal of thoracic and cardiovascular surgery》1986,92(1):1-5
Technical details of investigational orthotopic cardiac transplantation for management of hypoplastic left heart syndrome in a neonate are presented. Extracorporeal perfusion technique and need for extensive aortic arch reconstruction are emphasized. Although this experience was with a subhuman primate (baboon) donor, source of donor graft makes little difference with regards to the unique technical aspects of cardiac transplantation in a ductus-dependent newborn infant with a diminutive aortic arch. 相似文献