全文获取类型
收费全文 | 866篇 |
免费 | 46篇 |
国内免费 | 35篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 69篇 |
妇产科学 | 4篇 |
基础医学 | 84篇 |
口腔科学 | 98篇 |
临床医学 | 112篇 |
内科学 | 161篇 |
皮肤病学 | 23篇 |
神经病学 | 15篇 |
特种医学 | 184篇 |
外科学 | 43篇 |
综合类 | 24篇 |
预防医学 | 40篇 |
眼科学 | 14篇 |
药学 | 41篇 |
中国医学 | 1篇 |
肿瘤学 | 29篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 9篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 18篇 |
2017年 | 14篇 |
2016年 | 12篇 |
2015年 | 19篇 |
2014年 | 16篇 |
2013年 | 26篇 |
2012年 | 17篇 |
2011年 | 10篇 |
2010年 | 44篇 |
2009年 | 38篇 |
2008年 | 13篇 |
2007年 | 19篇 |
2006年 | 22篇 |
2005年 | 36篇 |
2004年 | 19篇 |
2003年 | 4篇 |
2002年 | 15篇 |
2001年 | 16篇 |
2000年 | 13篇 |
1999年 | 20篇 |
1998年 | 49篇 |
1997年 | 51篇 |
1996年 | 48篇 |
1995年 | 33篇 |
1994年 | 44篇 |
1993年 | 38篇 |
1992年 | 16篇 |
1991年 | 23篇 |
1990年 | 12篇 |
1989年 | 25篇 |
1988年 | 49篇 |
1987年 | 21篇 |
1986年 | 21篇 |
1985年 | 35篇 |
1984年 | 9篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 6篇 |
1976年 | 12篇 |
1975年 | 4篇 |
排序方式: 共有947条查询结果,搜索用时 11 毫秒
141.
Objectives
The aim of the study was to evaluate the impact of different patterns of nonadherence on treatment outcomes in patients with long‐term follow‐up.Methods
This cohort study included patients who began highly active antiretroviral therapy during 1996–1999, with the last follow‐up in 2007. Adherence was evaluated every 2 months by monitoring of pharmacy refills and by using self‐reports. Patients were considered nonadherent at a specific visit when less than 90% of the prescribed drugs had been taken. Adherence was categorized as follows. (A) Continuous adherence: a patient had to be adherent in all of the evaluations throughout the period of follow‐up. (B) Treatment interruption: drugs were not taken for more than 3 days, for any reason. Treatment failure was defined as viral load >500 HIV‐1 RNA copies/mL or death. Cox proportional risk models were used to calculate adjusted relative hazards (ARHs) of treatment failure.Results
A total of 540 patients were included in the study, with a median follow‐up of 8.3 years. Only 32.78% of patients achieved and maintained continuous adherence, and 42.78% of patients had treatment interruptions. Noncontinuous adherence [ARH 1.48; 95% confidence interval (CI) 1.02–2.14] and treatment interruptions (ARH 1.39; 95% CI 1.04–1.85) were associated with treatment failure for the overall cohort; however, for patients with more than 3 years of follow‐up, only treatment interruptions were independently associated with treatment failure.Conclusions
Only one‐third of patients managed to achieve continuous adherence, and almost half of the patients had treatment interruptions, which have a particularly marked effect on treatment outcomes over the long term.142.
Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants 总被引:10,自引:0,他引:10
Kawamura T Cohen SS Borris DL Aquilino EA Glushakova S Margolis LB Orenstein JM Offord RE Neurath AR Blauvelt A 《The Journal of experimental medicine》2000,192(10):1491-1500
Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1(Ba-L) infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08-4.77%). HIV-1-infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1-1 microg HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1(Ba-L) (an R5 HIV-1 strain) more efficiently infected LC-T cell cocultures when compared with HIV-1(IIIB) (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testing of agents designed to block sexual transmission of HIV-1. 相似文献
143.
Hao Feng Ai-Guo Lu Xue-Wei Zhao Ding-Pei Han Jing-Kun Zhao Lei Shi Tobias S Schiergens Serene ML Lee Wen-Peng Zhang Wolfgang E Thasler 《World journal of gastroenterology : WJG》2015,21(23):7225-7232
AIM: To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer.METHODS: All the patients with rectosigmoid carcinoma who underwent laparoscopic radical surgical resection in the Shanghai Minimally Invasive Surgical Center at Ruijin Hospital affiliated to Shanghai Jiao-Tong University between October 2009 and October 2013 were included in this study. Twenty-six cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected. Symptoms, endoscopic findings and clinicopathological characteristics were evaluated retrospectively.RESULTS: There were no significant differences between patients with and without schistosomiasis in gender, age, CEA, CA19-9, preoperative biopsy findings or postoperative pathology. Patients with rectosigmoid schistosomiasis had a significantly higher CA-125 level and a larger proportion of these patients were at an early tumor stage (P = 0.003). Various morphological characteristics of schistosomiasis combined with rectosigmoid cancer could be found by colonoscopic examination: 46% were fungating mass polyps, 23% were congestive and ulcerative polyps, 23% were cauliflower-like masses, 8% were annular masses. Only 27% of the patients were diagnosed with rectal carcinoma preoperatively after the biopsy. Computed tomography (CT) scans showed thickened intestinal walls combined with linear and tram-track calcifications in 26 patients.CONCLUSION: Rectosigmoid carcinoma combined with schistosomiasis is associated with higher CA-125 values and early tumor stages. CA-125 and CT scans have a reasonable sensitivity for the accurate diagnosis. 相似文献
144.
The effect of in vitro human immunodeficiency virus infection on dendritic-cell differentiation and function 总被引:2,自引:4,他引:2
Canque B; Rosenzwajg M; Camus S; Yagello M; Bonnet ML; Guigon M; Gluckman JC 《Blood》1996,88(11):4215-4228
CD1a+ dendritic cells (DC) differentiate from a major population of nonadherent CD13(hi)lin- cells that appear when human cord blood CD34+ hematopoietic progenitor cells are cultured with stem-cell factor, granulocyte/macrophage (MA) colony-stimulating factor, and tumor necrosis factor-alpha (TNF-alpha) for 5 days. CD13hilin- cells, which also comprise MA and granulocyte precursors, are CD4+ and can thus be targets of human immunodeficiency virus (HIV). Low replication was noted when these day 5 cells were infected with lymphotropic HIV-1LA1 (p24: < or = 4 ng/mL on day 8 postinfection [PI]), while high virus production occurred with MA-tropic HIV-1Ba-L, HIV-1Ada, or HIV-1-m-n. (p24: 50 to > or = 1,000 ng/mL). Strong cytopathicity (CPE) was then observed in nonadherent cells as in adherent MA. However, FACS analysis on day 7 PI showed that HIV did not affect differentiation of DC that survived CPE: apart from CD4 downmodulation related to HIV production, overall expression of CD40, CD80, and CD86 costimulatory molecules, and of HLA-DR, was unchanged relative to controls. At that time, the capacity of DC from HIV-infected cultures to stimulate the mixed leukocyte reaction was only altered less than 10-fold. Immunocytochemistry on day 7 PI showed that most HIV-infected cells were included in syncytia that were stained by anti-CD1a, anti-S100, and anti-CD14 antibodies, indicating that syncytia consisted of DC and cells of the MA lineage. Polymerase chain reaction analysis of FACS- sorted CD1a+ cells confirmed that they harbored then HIV DNA. Viral DNA was also detected in CD1a+ DC from noninfected cultures that had been exposed to HIV only after sorting. Therefore, we examined whether in infected cultures DC precursors were infected at the onset or if virus spread later from other infected cells to differentiated DC. This was answered by showing that, 24 hours postexposure to HIV, viral DNA was preferentially detected in day 5 sorted CD13hilin- versus CD13hilin- cells, and that it was found in the CD1a+ progeny of CD13(hi)lin- cells 48 hours later. In addition, HIV replication did not affect myeloid clonogenic progenitors in day 0 to day 7 PI cultures, although viral DNA was detected in colony-forming unit-granulocyte/macrophage (CFU- GM)/CFU-M colonies derived from day 3 and 7 PI cultures. Thus, precursors of DC and their progeny are susceptible to HIV in vitro, but, apart from CPE, the effect of virus production on DC differentiation or function is limited. 相似文献
145.
Chemoattractant-induced changes in surface expression and redistribution of a functional ligand for P-selectin on neutrophils 总被引:4,自引:0,他引:4
Adhesion between platelets and neutrophils is mediated through the interaction of P-selectin on activated platelets with a carbohydrate- containing structure on neutrophils, and occurs under both static and shear conditions. Recent studies using flow chambers have shown that neutrophils become activated after binding to surface-adherent platelets expressing P-selectin. The objective of the present study was to investigate the effect of such activation on the interactions of platelet P-selectin with its ligand on neutrophils. Flow cytometric analyses using P-selectin chimeras revealed that activation induced a rapid and marked reduction in chimera binding, with levels of binding decreased by 71% after 15 minutes of stimulation with the chemotactic agent, FMLP. Using a visual assay of platelet-neutrophil rosetting, we showed that the P-selectin ligand was translocated and clustered at the uropod of neutrophils following the shape changes and polarization induced by chemotactic stimulation. Activated neutrophils bound to surface-adherent platelets also displayed the clustering of P-selectin ligand at the uropod, and these neutrophils detached from the platelets when a shear stress (2 dynes/cm2) was applied through the adhesion chamber. These results indicate that chemotactic stimulation of neutrophils induces changes in the surface expression and distribution of a biologically relevant ligand for P-selectin, and that these changes might influence the adhesive interactions occurring between neutrophils and activated platelets. 相似文献
146.
B-cell acute lymphoblastic leukemia (B-ALL), more frequently than any other B-lineage neoplasm, exhibits oligoclonal Ig heavy chain (IgH) gene rearrangement in 15% to 43% of all cases studied. To study the molecular processes that promote multiple IgH rearrangements, a comprehensive sequence analysis of a B-ALL case was performed in which seven clonal IgH gene rearrangements were identified. The genetic profiles suggested that a single leukemic progenitor clone evolved into several subclones through dual processes of variable (VH) to preexisting diversity-joining (DJH) gene segment rearrangement and VH to VH gene replacement. Predominant IgH-V usage and the uniquely rearranged clonotype-specific VHDJH region gene sequences were identified using a novel DNA-based gene amplification strategy. Polymerase chain reaction (PCR) was directed by an IgH-J generic primer and a complement of family-specific IgH-V primers that defined the major B-cell IgH-V gene usage. Clonality of rearranged VHDJH bands was substantiated by high resolution denaturant gel electrophoretic analysis. Sequence patterns of the amplified VHDJH fragments segregated into two groups defined by common DJH sequences. Partial N region homology at the VHD junction as well as shared DJH sequences firmly established VH to VHDJH gene replacement as a mechanism generating clonal evolution in one group. In the second subset, oligoclonality was propagated by independent VH gene rearrangements to a common DJH precursor. The contributions of all clonal Ig-VHDJH repertoires for each group was approximately 50% and reflected a symmetric distribution of leukemic subclones generated by either process. Thus, oligoclonal rearrangements evolved by two independent, yet seemingly contemporaneous molecular genetic mechanisms. All seven clones displayed nonfunctional Ig-VHDJH recombinations. These observations may have relevance to the recombinatorial opportunities available during normal B-cell maturation. 相似文献
147.
Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission 总被引:2,自引:0,他引:2
Locasciulli A; Gornati G; Tagger A; Ribero ML; Cavalletto D; Cavalletto L; Masera G; Shulman HM; Portmann B; Alberti A 《Blood》1991,78(6):1619-1622
Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho- enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off- therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia. 相似文献
148.
Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease 总被引:5,自引:0,他引:5
Mannucci PM; Lattuada A; Castaman G; Lombardi R; Colibretti ML; Ciavarella N; Rodeghiero F 《Blood》1989,74(7):2433-2436
To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD. 相似文献
149.
150.
Auber ML; Horwitz LJ; Blaauw A; Khorana S; Tucker S; Woods T; Warmuth M; Dicke KA; McCredie KB; Spitzer G 《Blood》1988,71(1):166-172
Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL. 相似文献