全文获取类型
收费全文 | 4042篇 |
免费 | 328篇 |
国内免费 | 24篇 |
专业分类
耳鼻咽喉 | 35篇 |
儿科学 | 151篇 |
妇产科学 | 61篇 |
基础医学 | 733篇 |
口腔科学 | 32篇 |
临床医学 | 456篇 |
内科学 | 847篇 |
皮肤病学 | 66篇 |
神经病学 | 492篇 |
特种医学 | 74篇 |
外科学 | 443篇 |
综合类 | 14篇 |
一般理论 | 2篇 |
预防医学 | 366篇 |
眼科学 | 42篇 |
药学 | 281篇 |
中国医学 | 9篇 |
肿瘤学 | 290篇 |
出版年
2024年 | 2篇 |
2023年 | 38篇 |
2022年 | 45篇 |
2021年 | 101篇 |
2020年 | 60篇 |
2019年 | 102篇 |
2018年 | 111篇 |
2017年 | 72篇 |
2016年 | 81篇 |
2015年 | 105篇 |
2014年 | 154篇 |
2013年 | 204篇 |
2012年 | 312篇 |
2011年 | 342篇 |
2010年 | 172篇 |
2009年 | 171篇 |
2008年 | 291篇 |
2007年 | 290篇 |
2006年 | 289篇 |
2005年 | 282篇 |
2004年 | 262篇 |
2003年 | 280篇 |
2002年 | 223篇 |
2001年 | 31篇 |
2000年 | 20篇 |
1999年 | 35篇 |
1998年 | 41篇 |
1997年 | 51篇 |
1996年 | 31篇 |
1995年 | 23篇 |
1994年 | 31篇 |
1993年 | 33篇 |
1992年 | 8篇 |
1991年 | 14篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 13篇 |
1985年 | 2篇 |
1984年 | 12篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有4394条查询结果,搜索用时 15 毫秒
131.
132.
Henry C M'Baïlara K Desage A Gard S Misdrahi D Vieta E 《Journal of affective disorders》2007,101(1-3):35-41
BACKGROUND: DSM-IV criteria for mixed states may be too restrictive and may actually exclude patients who do not meet the full criteria for a manic and depressive state. Using this DSM-IV definition, many patients who are considered depressed may have mixed features, which can explain why some bipolar depressive states can worsen with antidepressants and can be improved by mood stabilizers or atypical antipsychotics. A dimensional approach not exclusively focused on the tonality of affect would help to define a broader entity of mixed states. The aim of this study was to apply a dimensional model to bipolar episodes and to assess the overlap between the groups defined using this model and using categorical diagnosis. METHOD: We assessed 139 DSM-IV acutely ill bipolar I patients with MAThyS (Multidimensional Assessment of Thymic States by Henry et al. in press), a scale that assesses five quantitative dimensions exploring excitatory and inhibition processes, and that is not focused on tonality of mood but on emotional reactivity. We studied the relationship between clusters defined by statistical analyses and DSM-IV bipolar mood states. RESULTS: This study showed the existence of three clusters. Cluster 1 was characterized by an inhibition in all dimensions and corresponded to the depressive cluster (more than 90% of patients met the criteria for DSM-IV Major Depressive Episode (MDE)). Cluster 2 showed a general excitation and was mainly DSM-IV manic or hypomanic patients (90%). Cluster 3 (Mixed) was more complex and the diagnosis included MDE (56%) in most of the cases associated with manic or hypomanic symptoms, mixed states (18%) defined by DSM-IV criteria, and manic or hypomanic states (25%). Emotional reactivity was relevant to distinguish Cluster 1 (Depressive), exhibiting emotional hypo-reactivity, from Cluster 2 (Manic) and 3 (Mixed), characterized by emotional hyper-reactivity. Sadness was reported equally in all three clusters. CONCLUSION: A dimensional approach using the concept of emotional reactivity seems appropriate to define a broad mixed state entity in patients who would be diagnosed with MDE according to DSM-IV. Further studies are needed to test the relevance of this model in therapeutic strategies. 相似文献
133.
Bacterial infections in the gastrointestinal tract represent a major global health problem, even in the presence of normally effective mucosal immune mechanisms. Milk fermented by Lactobacillus helveticus R389 (FM) or its non-bacterial fraction obtained by milk fermentation at controlled pH 6 (NBF) are able to activate the small intestine mucosal immune response according to previous studies. In this work we aimed at comparing their protection capacity against an infection by Salmonella enteritidis serovar Typhimurium and at studying the mechanisms involved. In a completely randomized design, BALB/c mice received FM or NBF for 2, 5 or 7 consecutive days, followed by a single oral challenge with S. Typhimurium (10(7) cells/mouse). The increase in the number of IgA+ cells in the lamina propria of the small intestine, after the feeding periods, was accompanied by an increase in the luminal content of total S-IgA. However, no antibodies were produced against the NBF. In mice given the FM or the NBF for 7 consecutive days, lower levels of liver colonization on day 7 post-challenge with S. Typhimurium, higher luminal contents of specific anti-Salmonella S-IgA, higher percentages of survival to infection and lower numbers of MIP-1alpha+ cells in the lamina propria were observed. In this work we observed that in both the FM or the NBF there are active principles that confer enhanced protection against S. Typhimurium infection. However, the mechanisms underlying mucosal immunomodulation and protection are different. In those mechanisms, the mucosal immune response would seem to be more involved than the competitive or exclusion mechanisms between L. helveticus R389 and S. enteritidis serovar Typhimurium. 相似文献
134.
Kanamaru Y Arcos-Fajardo M Moura IC Tsuge T Cohen H Essig M Vrtovsnik F Loirat C Peuchmaur M Beaudoin L Launay P Lehuen A Blank U Monteiro RC 《European journal of immunology》2007,37(4):1116-1128
Myeloid cells bear Fc receptors (FcR) that mediate inflammatory signaling through the ITAM-containing FcRgamma adaptor. They express FcRgamma-associated FcalphaRI, which modulate either activating or inhibitory signaling depending on the type of ligand interaction. The role of FcalphaRIgamma in disease progression remains unknown, notably in IgA nephropathy (IgAN), one of major causes of end-stage renal disease, in which large amounts of circulating IgA-immune complexes (IC) may mediate receptor activation. To analyze the involvement of FcalphaRI activation in glomerulonephritis (GN), we generated Tg mice expressing a mutated, signaling-incompetent, human FcalphaRI(R209L) that cannot associate with FcRgamma. Like FcalphaRI(wt)-Tg mice, they developed mesangial IgA deposits but not macrophage infiltration. FcalphaRI activation in FcalphaRI(wt), but not in FcalphaRI(R209L), Tg mice resulted in marked inflammation with severe proteinuria and leukocyte infiltration in spontaneous IgAN or anti-glomerular basement membrane Ab-induced GN models. Receptor triggering of syngenically transferred FcalphaRI(wt) Tg macrophages into non-Tg animals induced their recruitment into injured kidneys during GN development. FcalphaRI(wt) cross-linking on macrophages activated MAP kinases and production of TNF-alpha and MCP-1. Moreover, IgA-IC from IgAN patients activated FcalphaRI and induced TNF-alpha production. Thus, FcalphaRI activation mediates GN progression by initiating a cytokine/chemokine cascade that promotes leukocyte recruitment and kidney damage. 相似文献
135.
Activity of Indatuximab Ravtansine against Triple-Negative Breast Cancer in Preclinical Tumor Models
Kurt Schönfeld Peter Herbener Chantal Zuber Thomas Häder Katrin Bernöster Christoph Uherek Jörg Schüttrumpf 《Pharmaceutical research》2018,35(6):118
Purpose
Triple-negative breast cancer (TNBC) is related with a poor prognosis as patients do hardly benefit from approved therapies. CD138 (Syndecan-1) is upregulated on human breast cancers. Indatuximab ravtansine (BT062) is an antibody-drug-conjugate that specifically targets CD138-expressing cells and has previously shown clinical activity in multiple myeloma. Here we show indatuximab ravtansine as a potential mono- and combination therapy for TNBC.Methods
The effects of indatuximab ravtansine were assessed in vitro in SK-BR-3 and T47D breast cancer cell lines. The in vivo effects of indatuximab ravtansine alone and in combination with docetaxel or paclitaxel were assessed in MAXF401, MAXF1384 and MAXF1322 xenograft TNBC models.Results
CD138+ SK-BR-3 and T47D cells were highly sensitive to indatuximab ravtansine. The high CD138-expressing MAXF401 xenograft model demonstrated strong inhibition of tumor growth with 4 mg/kg indatuximab ravtansine. High doses of indatuximab ravtansine (8 mg/kg), docetaxel and the combination of both led to complete remission. In the low CD138-expressing MAXF1384 xenograft model, only combination of indatuximab ravtansine and docetaxel demonstrated a significant efficacy. In the MAXF1322 xenograft model, indatuximab ravtansine alone and in combination with paclitaxel elicited complete remission.Conclusions
These data demonstrate potential use of indatuximab ravtansine in combination with docetaxel or paclitaxel for CD138-positive TNBC.136.
Julia?BaudryEmail author Hélène?Lelong Solia?Adriouch Chantal?Julia Benjamin?Allès Serge?Hercberg Mathilde?Touvier Denis?Lairon Pilar?Galan Emmanuelle?Kesse-Guyot 《European journal of nutrition》2018,57(7):2477-2488
Purpose
Metabolic syndrome (MetS), a multicomponent condition, is a cardiovascular disease predictor. Although exposure to agricultural pesticides has been suggested as a potential contributor to the rising rates of obesity, type 2 diabetes, and other features of metabolic disorders, no studies have focused on the association between consumption of organic food (produced without synthetic pesticides) and MetS. We aimed to investigate the cross-sectional association between organic food consumption and MetS in French adults to determine whether it would be worth conducting further studies, particularly large prospective and randomised trials.Methods
A total of 8174 participants from the NutriNet-Santé study who attended a clinical visit and completed an organic food frequency questionnaire were included in this cross-sectional analysis. We evaluated the association between the proportion of organic food in the diet (overall and by food group) and MetS using Poisson regression models while adjusting for potential confounders.Results
Higher organic food consumption was negatively associated with the prevalence of MetS: adjusted prevalence ratio was 0.69 (95% CI 0.61, 0.78) when comparing the third tertile of proportion of organic food in the diet with the first one (p value <0.0001). Higher consumption of organic plant-based foods was also related to a lower probability of having MetS. In addition, when stratifying by lifestyle factors (nutritional quality of the diet, smoking status, and physical activity), a significant negative association was detected in each subgroup (p values <0.05), except among smokers.Conclusions
Our results showed that a higher organic food consumption was associated with a lower probability of having MetS. Additional prospective studies and randomised trials are required to ascertain the relationship between organic food consumption and metabolic disorders.137.
Herberz Chantal Steidl Ralph Werner Pascal Hagen Julia 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2018,61(3):298-303
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Digitale Gesundheitsprodukte und -dienstleistungen beginnen sowohl die Versorgung von Kranken als auch die Prävention... 相似文献
138.
Chantal M. Koolhaas K. Dhana F. J. A. van Rooij J. D. Schoufour A. Hofman O. H. Franco 《The journal of nutrition, health & aging》2018,22(2):246-253
Objectives
Physical activity (PA) is associated with health-related quality of life (HRQL). The specific PA types that provide beneficial effects in an older population remain unclear. We assessed the association of total PA, walking, cycling, domestic work, sports and gardening with HRQL in middle-aged and elderly adults.Design
Cross-sectional study.Setting
Rotterdam, the Netherlands.Participants
5,554 participants, with a mean age of 69 years.Measurements
Total PA was categorized in five groups to evaluate the dose-response effect of PA and specific PA types were categorized in tertiles. HRQL was measured with the EuroQoL 5-dimension. The outcome of every HRQL domain (i.e. mobility, self-care, daily activities, pain and mood) was expressed as having any problems versus not having problems. Logistic and linear regression analyses were used, adjusting for confounders, to examine associations of total PA and PA types with HRQL domains.Results
In both middle-aged (<65 years) and elderly adults (>65 years), we found a dose-response association between total PA and better HRQL (i.e. lower odds of having problems in HRQL domains). In the middle-aged, sports was the only PA type associated with lower odds of having problems with all HRQL domains. In the elderly, all PA types were associated with less problems with HRQL domains, but cycling contributed most to the beneficial effect.Conclusions
Total PA was associated with better HRQL. Sports and cycling were the activity types that contributed most to this association in the middle-aged and elderly, respectively. Since PA levels tend to decline with aging, cycling and sports should be promoted with the aim to improve HRQL.139.
Rémy De Mil Elodie Guillaume Lydia Guittet Olivier Dejardin Véronique Bouvier Carole Pornet Véronique Christophe Annick Notari Hélène Delattre-Massy Chantal De Seze Jérôme Peng Guy Launoy Célia Berchi 《Value in health》2018,21(6):685-691
Background
Patient navigation programs to increase colorectal cancer (CRC) screening adherence have become widespread in recent years, especially among deprived populations.Objectives
To evaluate the cost-effectiveness of the first patient navigation program in France.Methods
A total of 16,250 participants were randomized to either the usual screening group (n = 8145) or the navigation group (n = 8105). Navigation consisted of personalized support provided by social workers. A cost-effectiveness analysis of navigation versus usual screening was conducted from the payer perspective in the Picardy region of northern France. We considered nonmedical direct costs in the analysis.Results
Navigation was associated with a significant increase of 3.3% (24.4% vs. 21.1%; P = 0.003) in participation. The increase in participation was higher among affluent participants (+4.1%; P = 0.01) than among deprived ones (+2.6%; P = 0.07). The cost per additional individual screened by navigation compared with usual screening (incremental cost-effectiveness ratio) was €1212 globally and €1527 among deprived participants. Results were sensitive to navigator wages and to the intervention effectiveness whose variations had the greatest impact on the incremental cost-effectiveness ratio.Conclusions
Patient navigation aiming at increasing CRC screening participation is more efficient among affluent individuals. Nevertheless, when the intervention is implemented for the entire population, social inequalities in CRC screening adherence increase. To reduce social inequalities, patient navigation should therefore be restricted to deprived populations, despite not being the most cost-effective strategy, and accepted to bear a higher extra cost per additional individual screened. 相似文献140.
High-affinity, human antibody-like antibody fragment (single-chain variable fragment) neutralizing the lethal factor (LF) of Bacillus anthracis by inhibiting protective antigen-LF complex formation 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Antimicrobial agents and chemotherapy》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Pelat T Hust M Laffly E Condemine F Bottex C Vidal D Lefranc MP Dübel S Thullier P 《Antimicrobial agents and chemotherapy》2007,51(8):2758-2764
The anthrax lethal toxin (LT) consists of two subunits, the protective antigen (PA) and the lethal factor (LF), and is essential for anthrax pathogenesis. Several recombinant antibodies directed against PA and intended for medical use have been obtained, but none against LF, despite the recommendations of anthrax experts. Here we describe an anti-LF single-chain variable fragment (scFv) that originated from an immunized macaque (Macaca fascicularis) and was obtained by phage display. Panning of the library of 1.8 x 10(8) clones allowed the isolation of 2LF, a high-affinity (equilibrium dissociation constant, 1.02 nM) scFv, which is highly neutralizing in the standardized in vitro assay (50% inhibitory concentration, 1.20 +/- 0.06 nM) and in an in vivo assay. The scFv neutralizes anthrax LT by inhibiting the formation of the LF-PA complex. The genes encoding 2LF are very similar to those of human immunoglobulin germ line genes, sharing substantial (84.2%) identity with their most similar, germinally encoded counterparts; this feature favors medical applications. These results, and others formerly published, demonstrate that our approach can generate antibody fragments suitable for prophylaxis and therapeutics. 相似文献