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目的 探讨巨细胞病毒(CMV)肝炎患儿血清干扰素-γ(IFN-γ)和白细胞介素-18(IL-18)水平变化及其与预后的关系。方法 2017年1月~2019年6月我院收治的95例CMV肝炎患儿(轻症66例,重症29例)和90例健康儿童,给予CMV肝炎儿童更昔洛韦治疗6 w,采用ELISA法检测血清IFN-γ和IL-18水平。应用受试者工作特征曲线下面积(AUROC)分析血清细胞因子预测CMV肝炎患儿的转归。结果 轻症CMV肝炎患儿血清IFN-γ、IL-18、ALT和TBIL水平分别为(7.7±2.9)mmol/L、(56.9±5.7)pg/L、(69.8±11.3)U/L和(75.4±16.7)μmol/L,重症CMV肝炎患儿分别为(16.6±4.1)mmol/L、(89.5±8.3)pg/L、(104.7±13.2)U/L和(235.7±20.4)μmol/L,均显著高于健康儿童【分别为(2.1±1.1)mmol/L、(33.7±4.9)pg/L、(19.6±3.1)U/L和(8.3±2.7)μmol/L, P<0.05】;在治疗后,轻症CMV肝炎患儿血清IFN-γ、IL-18、ALT和TBIL水平分别为(2.2±0.9)mmol/L、(34.1±5.4)pg/L、(21.2±4.3)U/L和(13.4±4.1)μmol/L,显著低于重症CMV肝炎患儿【(4.1±0.6)mmol/L、(40.6±7.9)pg/L、(46.5±7.5)U/L和(26.5±3.4)μmol/L,P<0.05】;在95例患儿中,痊愈80例,未恢复15例;有效患儿血清IFN-γ、IL-18、ALT和TBIL水平显著低于无效患儿,差异有统计学意义(均P<0.05);以血清IFN-γ预测CMV肝炎不良转归(无效)的敏感度为86.7%,特异性为96.3%,血清IL-18预测的敏感度为93.3%,特异性为73.8%。结论 CMV肝炎患儿血清IFN-γ和IL-18水平明显升高,在治疗后其血清水平下降缓慢者,可能预后不良,值得进一步监测。  相似文献   
4.
《Vaccine》2021,39(40):5729-5731
IntroductionConcerns were raised over an increase in Bell's palsy, herpes simplex and herpes zoster after BNT162b2 vaccination, all are manifestations of herpesviruses reactivation. As herpesviruses commonly reactivate in the oropharynx, we have hypothesized that oropharyngeal shedding of herpesviruses will increase after vaccination.MethodsImmune-competent Adults, excluding those using topical steroids or manifesting symptomatic herpesvirus infection, were sampled before BNT162b2 vaccination and one week after. Herpesviruses 1–7 shedding was tested with a multiplexed PCR.ResultsIn 103 paired samples the prevalence of herpesviruses was similar before and after vaccination: HSV1, 3.9% vs. 5.8% (p = 0.75); HSV2, 0% vs. 1% (p = not applicable, NA); VZV, 0% vs. 0% (p = NA); EBV, 14.6% vs. 17.5% (p = 0.63); CMV, 0% vs. 0% (p = NA); HHV6, 4.9% vs. 7.8% (p = 0.55); HHV7, 71.8% vs. 72.8% (p = 1); any herpesvirus, 73.8% vs. 74.8% (p = 1).DiscussionWe did not find evidence for increased oropharyngeal reactivation of herpesviruses one week after BNT162b2.  相似文献   
5.
《Vaccine》2019,37(44):6696-6706
Live attenuated viral vaccine/vector candidates are inherently unstable and infectivity titer losses can readily occur without defining appropriate formulations, storage conditions and clinical handling practices. During initial process development of a candidate vaccine against HIV-1 using a recombinant Human Cytomegalovirus vector (rHCMV-1), large vector titer losses were observed after storage at 4 °C and after undergoing freeze-thaw. Thus, the goal of this work was to develop candidate frozen liquid formulations of rHCMV-1 with improved freeze-thaw and short-term liquid stability for potential use in early clinical trials. To this end, a virus stability screening protocol was developed including use of a rapid, in vitro cell-based immunofluorescence focus assay to quantitate viral titers. A library of ∼50 pharmaceutical excipients (from various known classes of additives) were evaluated for their effect on vector stability after freeze-thaw cycling or incubation at 4 °C for several days. Certain additives including sugars and polymers (e.g., trehalose, sucrose, sorbitol, hydrolyzed gelatin, dextran 40) as well as removal of NaCl (lower ionic strength) protected rHCMV-1 against freeze-thaw mediated losses in viral titers. Optimized solution conditions (e.g., solution pH, buffers and sugar type) slowed the rate of rHCMV-1 titer losses in the liquid state at 4 °C. After evaluating various excipient combinations, three new candidate formulations were designed and rHCMV-1 stability was benchmarked against both the currently-used and a previously reported formulation. The new candidate formulations were significantly more stable in terms of reducing rHCMV-1 titer losses after 5 freeze-thaw cycles or incubation at 4 °C for 30 days. This case study highlights the utility of semi-empirical design of frozen liquid formulations of a live viral vaccine candidate, where protection against infectivity titer losses due to freeze-thaw and short-term liquid storage are sufficient to enable more rapid initiation of early clinical trials.  相似文献   
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Purpose: To report long-term outcomes of topical ganciclovir (GCV) and corticosteroids in Korean patients with cytomegalovirus (CMV) corneal endotheliitis.

Methods: This retrospective study included 13 eyes from 13 patients with CMV corneal endotheliitis, with a follow-up period of 24.5 ± 8.2 months. The patients were consistently maintained with topical 2% GCV and 1% prednisolone acetate eyedrop.

Results: All patients demonstrated unilateral typical coin-shaped keratic precipitates (KPs) or linear KP, and positive CMV polymerase chain reaction of aqueous humor. After 2 weeks of treatment, all patients showed decrease of clinical signs. During the follow-up, four patients developed mild anterior chamber inflammation with increased intraocular pressure without typical coin-shaped KPs or edema, started to use the initial dose, and resolved the clinical signs. One patient showed recurrence of corneal edema twice, and was administered systemic valgancyclovir for 2 weeks upon second recurrence with resolution of clinical signs.

Conclusion: Long-term maintenance therapy with topical GCV and corticosteroids are effective and maintain corneal endothelial function in Korean patients with CMV endotheliitis.  相似文献   
7.
Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease(IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.  相似文献   
8.
Objective/BackgroundCytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT.MethodsWe conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity.ResultsIn multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00–1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83–2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor–recipient mismatch (HR = 1.05; 95% 95% CI, 0.66–1.68; p = .83 and HR = 0.94; 95% CI, 0.51–1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79–1.31; p = .89 and HR = 0.89; 95% CI, 0.65–1.22; p = .47, respectively).ConclusionThese findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT.  相似文献   
9.
Abstract

Background: Cytomegalovirus (CMV) is rarely thought to be the cause of significant gastrointestinal infection in immunocompetent children. CMV colitis is seldom observed in young infants. This study aims to examine the clinical features of CMV colitis in Chinese children.

Methods: Patients with infantile onset CMV colitis diagnosed in intestinal tissue at Children’s Hospital of Fudan University from 1st January 2017, to 31st January 2019 were enrolled. Clinical data were retrieved from medical records, and the literature on infant CMV colitis was also reviewed.

Results: Ten patients were included with a median age of 2.5?months [interquartile range 2.0, 6.3?months]. All 10 patients had diarrhea, 10 patients had anemia, seven patients reported hematochezia, five patients had hypoalbuminemia, five patients had retinitis, two patients had hearing impairment, and one patient had perianal abscess and anal fistula. The patients had punched-out ulcerations, longitudinal ulcerations or irregular ulcerations on the rectum and/or colon. Typical histologic evaluation showed crypt distortion and inflammatory infiltration. CMV inclusion bodies were noted in four patients. Immunohistochemistry on intestinal tissue was performed to diagnose CMV, with all patients positive. After follow-up, all patients are clinically recovered or in remission; six patients received antiviral therapy, and five patients had healed ulcers on endoscopic examination.

Conclusions: CMV colitis might be a rare cause of intractable diarrhea in immunocompetent children. Clinicians should be aware of the possibility of CMV colitis in patients with intractable diarrhea.  相似文献   
10.
Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival.Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection.The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials.Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology.  相似文献   
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