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41.
Wenjing Tang Ying Dou Tao Qin Yuan Ding Xuemei Tang Xiaodong Zhao Yunfei An 《Scandinavian journal of immunology》2019,89(6)
DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8+ T‐cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. We analysed BCR characteristics, including somatic hypermutation (SHM) frequency, using deep sequencing of multiplex PCR products derived from BCR heavy chain CDR3 regions from DIDS patients and controls. The antibody avidity of human tetanus and hemophilus influenza B antibodies was determined by ELISA using thiocyanate elution. IVIG replacement treatment and infection conditions were investigated retrospectively. We found skewing of the BCR repertoire and decreased antibody avidity in patients with DIDS. DIDS patients had fewer negatively charged amino acids than healthy controls. The SHM frequency of the IGHV3 gene was lower in patients with DIDS. Patients received regular IVIG therapy, resulting in fewer and less severe infections. We conclude that although IgG levels are normal in most DIDS patients, IVIG replacement therapy is still necessary. 相似文献
42.
Luis Veloza Cristina Teixido Natalia Castrejon Fina Climent Ana Carri Marta Marginet Davide Soldini Blanca Gonzlez‐Farr Inmaculada Ribera‐Cortada Armando Lopez‐Guillermo Eva Gonzlez‐Barca Adriana Sierra Mileyka Herrera Cndida Gmez Adriana Garcia Olga Balagu Elias Campo Antonio Martinez 《Histopathology》2019,75(6):799-812
43.
Puerarin (PR), a natural isoflavone isolated from Chinese traditional plant pueraria lobata, has attracted considerable attention due to its important biological and pharmacological activities. However, its effects on lesion of peri-implant and related mechanism of action are still not clear, which require further investigation. In this study, we evaluated the effects of PR on polymethylmethacrylate (PMMA)-induced lesion of peri-implant in vitro and in vivo, and explored its possible mechanism of action. Our results indicated that PR could inhibit PMMA-induced osteoclastogenesis in RAW264.7 cells with a dose-dependent manner in vitro and effectively down-regulate mRNA and protein expressions of matrix metalloprotein 9 (MMP-9), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and receptor activator of nuclear factor (NF)-κB (RANK), primarily via the suppression of NF-κB signaling. Furthermore, we found that PMMA induction could directly cause the phosphorylation of IκB and significantly promote the nuclear translocation of p65 in RAW264.7 cells. In other words, PR was able to dose-dependently attenuate the PMMA-induced nuclear translocation of p65 in RAW264.7 cells. In vivo, PR was observed to attenuate PMMA-induced osteoclastogenesis, osteolysis, mRNA expressions of receptor activator of nuclear factor (NF)-κB ligand (RANKL) and RANK, as well as protein levels of MMP-9, TNF-α, IL-6, and p65 in a murine calvarial osteolysis model. These findings suggested that PR might be a potential therapeutic drug to lesion of peri-implant, and provided new insights for understanding its possible mechanism. 相似文献
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47.
《Vaccine》2019,37(35):5059-5066
Background: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children.Methods: A cross-sectional multi-stage cluster survey was conducted among children born during 2010–2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis.Findings: A total of 2,520 children 5–7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%–5.45%) among mothers and 0.56% (95%CI: 0.32%–0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%–14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%–18.11%).Interpretation: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030.Funding: As per sources of funding. 相似文献
48.
Stefan Scholz Florian Koerber Kinga Meszaros Rosa Maya Fassbender Bernhard Ultsch Robert R. Welte Wolfgang Greiner 《Vaccine》2019,37(12):1692-1701
Introduction
Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.Method
A bottom-up, model-based costing approach has been used to calculate the diagnose- and age-specific yearly lifetime costs of a hypothetical cohort of MenB-related IMD cases. Direct costs contain the treatment cost for the acute phase of the disease, long-term sequelae, costs for rehabilitation, and public health response. Indirect costs are calculated for the human-capital approach and the friction-cost approach considering productivity losses of patients or parents for the acute phase and long-term sequelae. Publicly available databases from the Federal Statistical Office, the SOEP panel data set, literature, and expert opinion were used as data sources. All future costs beyond the reference year of 2015 were discounted at 3%.Results
The total costs for the hypothetical cohort (343 patients) from a societal perspective are €19.6 million (€57,100/IMD case) using the friction-cost approach and €58.8 million (€171,000/IMD case) using the human-capital approach. Direct costs amount to €18.6 million or €54,300 €/case. Sequelae are responsible for 81% of the direct costs/case.Discussion
The elevated costs/MenB-related IMD case reflect the severity of the disease. The total costs are sensitive to the productivity-loss estimation approach applied. MenB is an uncommon but severe disease; The costs/case reflect the severity of the disease and is within the same magnitude as for human papilloma virus infections. The available literature on sequelae is due to the uncommonness limited and heterogeneous. 相似文献49.
Natalie J. Kingston Liriye Kurtovic Renae Walsh Carina Joe George Lovrecz Stephen Locarnini James G. Beeson Hans J. Netter 《Vaccine》2019,37(12):1674-1684
The repetitive structure of compact virus-like particles (VLPs) provides high density displays of antigenic sequences, which trigger key parts of the immune system. The hepatitis B virus (HBV) and human papilloma virus (HPV) vaccines exploit the assembly competence of structural proteins, which are the effective immunogenic components of the prophylactic HBV and HPV vaccines, respectively. To optimize vaccine designs and to promote immune responses against protective epitopes, the “Asp-Ala-Asp-Pro” (NANP)-repeat from the Plasmodium falciparum circumsporozoite protein (CSP) was expressed within the exposed, main antigenic site of the small HBV envelope protein (HBsAgS); this differs from the RTS,S vaccine, in which CSP epitopes are fused to the N-terminus of HBsAgS. The chimeric HBsAgS proteins are assembly competent, produce VLPs, and provide a high antigenic density of the NANP repeat sequence. Chimeric VLPs with four or nine NANP-repeats (NANP4 and NANP9, respectively) were expressed in mammalian cells, the HBsAgS- and CSP-specific antigenicity of the VLPs was determined, and the immunogenicity of the VLPs assessed in relation to the induction of anti-HBsAgS and anti-CSP antibody responses. The chimeric VLPs induced high anti-CSP titres in BALB/c mice independent of the number of the NANP repeats. However, the number of NANP repeats influenced the activity of vaccine-induced antibodies measured by complement fixation to CSP, one of the proposed effector mechanisms for Plasmodium neutralization in vivo. Sera from mice immunized with VLPs containing nine NANP repeats performed better in the complement fixation assay than the group with four NANP repeats. The effect of the epitope-specific density on the antibody quality may instruct VLP platform designs to optimize immunological outcomes and vaccine efficacy. 相似文献
50.
《Vaccine》2019,37(24):3190-3198
The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined. 相似文献