全文获取类型
收费全文 | 1949篇 |
免费 | 122篇 |
国内免费 | 25篇 |
专业分类
耳鼻咽喉 | 19篇 |
儿科学 | 67篇 |
妇产科学 | 18篇 |
基础医学 | 271篇 |
口腔科学 | 167篇 |
临床医学 | 146篇 |
内科学 | 501篇 |
皮肤病学 | 81篇 |
神经病学 | 111篇 |
特种医学 | 87篇 |
外科学 | 229篇 |
综合类 | 17篇 |
预防医学 | 164篇 |
眼科学 | 27篇 |
药学 | 107篇 |
中国医学 | 9篇 |
肿瘤学 | 75篇 |
出版年
2023年 | 16篇 |
2022年 | 35篇 |
2021年 | 72篇 |
2020年 | 58篇 |
2019年 | 82篇 |
2018年 | 74篇 |
2017年 | 69篇 |
2016年 | 48篇 |
2015年 | 66篇 |
2014年 | 76篇 |
2013年 | 91篇 |
2012年 | 126篇 |
2011年 | 156篇 |
2010年 | 93篇 |
2009年 | 86篇 |
2008年 | 114篇 |
2007年 | 106篇 |
2006年 | 117篇 |
2005年 | 80篇 |
2004年 | 59篇 |
2003年 | 60篇 |
2002年 | 35篇 |
2001年 | 28篇 |
2000年 | 31篇 |
1999年 | 28篇 |
1998年 | 22篇 |
1997年 | 18篇 |
1996年 | 23篇 |
1995年 | 12篇 |
1994年 | 16篇 |
1993年 | 13篇 |
1992年 | 10篇 |
1991年 | 12篇 |
1990年 | 13篇 |
1989年 | 14篇 |
1988年 | 19篇 |
1987年 | 12篇 |
1986年 | 22篇 |
1985年 | 17篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1975年 | 3篇 |
1972年 | 4篇 |
1969年 | 2篇 |
1968年 | 3篇 |
排序方式: 共有2096条查询结果,搜索用时 31 毫秒
61.
Rodrigo Holanda Mendonça Ligia Maria Sotero Machado Carlos Otto Heise Graziela Jorge Polido Ciro Matsui André Macedo Serafim Silva Umbertina Conti Reed Edmar Zanoteli 《Neuromuscular disorders : NMD》2021,31(6):498-504
Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness and motor disability. The motor unit number index (MUNIX) is a biomarker used to assess loss of motor units in later-onset SMA patients. Twenty SMA patients (SMA types 3 and 4), aged between 7 and 41 years, were clinically evaluated through the Hammersmith Motor Functional Scale Expanded and the Spinal Muscular Atrophy-Functional Rating Scale. The patients underwent compound motor action potential (CMAP) and MUNIX studies of the right abductor pollicis brevis, abductor digiti minimi and tibialis anterior (TA) muscles. Age-matched healthy controls (n = 20) were enrolled to obtain normative CMAP and MUNIX values from the same muscles. Compared to healthy controls, SMA patients showed significant reductions in MUNIX values among all muscles studied, whereas CMAP showed reductions only in the weaker muscles (abductor digiti minimi and TA). MUNIX variability was significantly higher in the SMA group than in the control group. MUNIX variability in TA correlated with CMAP variability. Motor functional scores correlated with TA MUNIX. The MUNIX study is feasible in later-onset SMA patients, and TA MUNIX values correlate with disease severity in patients with mild motor impairment. 相似文献
62.
Warley Oliveira Silva Renata Perez Vianna Silva Macedo Giselle Nevares Renata Costa Val Rodrigues Juliana Francisca Grossi Heleno Andréa Vaz Braga Pintor Bernardo Mattos Almeida 《Journal of endodontics》2021,47(1):3-10
IntroductionThe management of endodontic emergencies has been particularly challenging during the coronavirus disease 2019 (COVID-19) outbreak because of the possible generation of airborne particles and aerosols. The aim of this report was to contribute to the practice of endodontics by proposing a general protocol for the management of emergencies showing the rationale for remote diagnosis, clinical procedures, and the use of personal protective equipment and barriers at the dental office during the COVID-19 outbreak.MethodsA review of the literature was conducted up to May 2020 on relevant institutional sites, aiming to retrieve the best updated evidence. The reporting considered the Reporting Tool for Practice Guidelines in Health Care statement.ResultsRecommendations from Cochrane Oral Health, the American Dental Association, and the Centers for Disease Control and Prevention were included along with the American Association of Endodontists resources and scientific articles that addressed the issue.ConclusionsThe proposed protocol could contribute to the management of endodontic emergencies at the dental office during the COVID-19 outbreak. 相似文献
63.
Salles Marcela Moreira Oliveira Viviane de Cássia Macedo Ana Paula do Nascimento Cássio Silva-Lovato Cláudia Helena Paranhos Helena de Freitas Oliveira 《Odontology / the Society of the Nippon Dental University》2021,109(1):284-294
Odontology - Evaluate, through a randomized clinical trial, the efficacy of brushing associated with oral irrigation in maintaining implant and overdenture hygiene. Thirty-eight participants, who... 相似文献
64.
Rodrigues Renata Prata Cunha Bernardes de Andrade Vieira Walbert Siqueira Walter Luiz Blumenberg Cauane de Macedo Bernardino talo Cardoso Srgio Vitorino Flores-Mir Carlos Paranhos Luiz Renato 《Clinical oral investigations》2020,24(7):2203-2217
Clinical Oral Investigations - To assess whether salivary urea and creatinine levels accurately reflect their serum levels in blood samples of adults to detect chronic kidney disease. A systematic... 相似文献
65.
Camile Ludovico Zamboti Carlos Augusto Marçal Camillo Amanda Paula Ricardo Rodrigues da Cunha Thaiuana Maia Ferreira Christiane Souza Guerino Macedo 《Revista brasileira de fisioterapia (S?o Carlos (S?o Paulo, Brazil))》2021,25(2):156-161
ObjectiveTo compare the performance, reliability, and validity of functional tests between women with and without patellofemoral pain.MethodsTwenty women with a diagnosis of patellofemoral pain between 18 and 40 years of age and 20 age-matched pain-free controls participated in the study. All participants performed a set of five function tests: sitting-rising test, sit-to-stand in 30 seconds, stair-climb test, stair descent test, and six-minute step test. To investigate reliability, participants were assessed on two different days, seven days apart, by two independent investigators blinded to the results of the other investigator. Validity was evaluated through associations with the results on the Anterior Knee Pain Scale.ResultsPerformance in the tests was worse in women with patellofemoral pain than in the control group for the sit-to-stand in 30 seconds (mean difference [MD] 3.4reps; 95%CI: 0.4, 6.4), stair-climb test (MD: 0.36 s; 95%CI: 0.1, 0.63), and six-minute step test (MD: 45reps; 95%CI: 20, 70). No differences were observed for the sitting-rising and stair descent tests. All tests in both groups showed moderate to excellent intra- and inter-rater reliability (intraclass correlation coefficients: 0.61 to 0.91 and 0.72 to 0.96, respectively). Finally, only the results on the sit-to-stand in 30 seconds test correlated with the Anterior Knee Pain Scale (r = 0.44, p = 0.047) in the patellofemoral pain group.ConclusionWomen with patellofemoral pain present lower performance on some functional tests. Functional tests are reliable in patients with patellofemoral pain, although they are not associated with the results on the Anterior Knee Pain Scale self-questionnaire. 相似文献
66.
Anna Luisa Kühn Jasmeet Singh Viraj M Moholkar Sudhakar R Satti Katyucia de Macedo Rodrigues Francesco Massari Matthew J Gounis Archie McGowan Ajit S Puri 《Interventional neuroradiology》2021,27(2):241
PurposeTo report use of distal radial artery (dRA) access for carotid artery stenting (CAS) and to discuss procedural setup and technical considerations for a successful intervention.MethodsA retrospective review of our prospective neurointerventional database of CAS was conducted between May 2019 and March 2020. All CAS cases via dRA in the anatomical snuffbox were identified. Patient demographics, clinical information, procedural and radiographic data was collected.Results22 CAS procedures in 20 patients via dRA were identified. Patients’ mean age was 69.4 years (range 53–87 years). 3 patients were female. Mean radial artery diameter was 2.1 mm (range 1.6–2.8 mm). dRA access was achieved in all cases. Conversion to femoral access was required in 2 cases (9.1%) due to persistent radial artery vasospasm resulting in patient discomfort despite multiple additional doses of intraarterial vasodilators and added intravenous sedation as well as tortuous vessel anatomy and limited support of the catheters in a type 3 aortic arch for left CAS.ConclusionOur preliminary experience with dRA access for CAS suggests this approach to be feasible and safe for patients. Technical considerations are important and preprocedural planning is necessary for a successful intervention. Catheter systems and devices specifically designed for radial access are needed to enable more interventionalists to safely perform neurointerventional procedures via wrist access. 相似文献
67.
Alexandre Braga Libório Marcelo Boecker Munoz Braz Antonio Carlos Seguro Gdayllon C. Meneses Fernanda Macedo de Oliveira Neves Danielle Carvalho Pedrosa Luciano Pamplona de Góes Cavalcanti Alice Maria Costa Martins Elizabeth de Francesco Daher 《The American journal of tropical medicine and hygiene》2015,92(3):611-616
Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P < 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P < 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage. 相似文献
68.
Macedo ME Lima MJ Silva AO Alcantara P Ramalhinho V Carmona J 《Journal of hypertension》2005,23(9):1661-1666
BACKGROUND: The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment and control in the Portuguese adult population. METHODS: This study was conducted in 2003, and a multistage cluster sampling method was used to select a national representative sample. A total of 5023 adults, age 18-90 years, were examined. Three blood pressure measurements were obtained by trained observers using an OMROM M4-I sphygmomanometer after a 5-min sitting rest. Information on the history of hypertension and the use of antihypertensive medications was obtained by use of a standard questionnaire. RESULTS: Hypertension was defined as a mean systolic blood pressure > or = 140 mmHg and/or diastolic blood pressure > or = 90 mmHg, or the use of antihypertensive medications. Overall, 42.1% of the Portuguese adult population aged 18-90 years, representing 3 311 830 people, had hypertension. The age-specific prevalence of hypertension in the three age groups studied--younger than 35 years, 35-64 years old and older than 64 years--was 26.2, 54.7 and 79% in men and 12.4, 41.1 and 78.7% in women, respectively. Among hypertensive patients, only 46.1% were aware of their high blood pressure, 39.0% were taking antihypertensive medication and 11.2% achieved blood pressure control (< 140/90 mmHg). CONCLUSIONS: Our results indicate that hypertension is highly prevalent in Portugal. The percentages of those with hypertension that are aware, treated and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection and treatment of hypertension in Portugal. 相似文献
69.
Benoit Desnues Amanda Beatriz Macedo Annie Roussel-Queval Johnny Bonnardel Sandrine Henri Olivier Demaria Lena Alexopoulou 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(4):1497-1502
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical presentations characterized by the presence of autoantibodies to nuclear components. Toll-like receptor (TLR)7, TLR8, and TLR9 sense microbial or endogenous nucleic acids and are implicated in the development of SLE. In mice TLR7-deficiency ameliorates SLE, but TLR8- or TLR9-deficiency exacerbates the disease because of increased TLR7 response. Thus, both TLR8 and TLR9 control TLR7 function, but whether TLR8 and TLR9 act in parallel or in series in the same or different cell types in controlling TLR7-mediated lupus remains unknown. Here, we reveal that double TLR8/9-deficient (TLR8/9−/−) mice on the C57BL/6 background showed increased abnormalities characteristic of SLE, including splenomegaly, autoantibody production, frequencies of marginal zone and B1 B cells, and renal pathology compared with single TLR8−/− or TLR9−/− mice. On the cellular level, TLR8−/− and TLR8/9−/− dendritic cells were hyperesponsive to TLR7 ligand R848, but TLR9−/− cells responded normally. Moreover, B cells from TLR9−/− and TLR8/9−/− mice were hyperesponsive to R848, but TLR8−/− B cells were not. These results reveal that TLR8 and TLR9 have an additive effect on controlling TLR7 function and TLR7-mediated lupus; however, they act on different cell types. TLR8 controls TLR7 function on dendritic cells, and TLR9 restrains TLR7 response on B cells.Systemic lupus erythematosus (SLE) is a complex chronic autoimmune disease that arises spontaneously and is characterized by production of autoantibodies against self-nucleic acids and associated proteins (1). These autoantibodies bind self-nucleic acids released by dying cells and form immune complexes that accumulate in different parts of the body, leading to inflammation and tissue damage. The kidneys, skin, joints, lungs, serous membranes, as well as, the cardiovascular, nervous and musculoskeletal system become targets of inflammation at onset or during the course of the disease (2). The etiology of SLE is unknown, yet genetics, sex, infectious agents, environmental factors, and certain medications may play a role in the initiation of the disease by causing alterations in lymphoid signaling, antigen presentation, apoptosis, and clearance of immune complexes (3, 4).Toll-like receptors (TLRs) detect specific microbial components widely expressed by bacteria, fungi, protozoa, and viruses, and initiate signaling pathways critical for induction of immune responses to infection (5). In contrast to the cell surface TLRs that detect bacterial cell wall components and viral particles, nucleic acid-sensing TLRs are localized mainly within endosomal compartments (6). Human endosomal TLRs consist of TLR3, which senses viral double-stranded RNA (dsRNA) (7), TLR7 and TLR8, which recognize viral single-stranded RNA (8–10), and TLR9, which detects bacterial and viral unmethylated CpG-containing DNA motifs (11). Interestingly, these endosomal TLRs are also able to detect self-nucleic acids (12–14). Although the endosomal localization isolate TLR3, TLR7, TLR8, and TLR9 away from self-nucleic acids in the extracellular space, still self-RNA or -DNA can become a potent trigger of cell activation when transported into TLR-containing endosomes, and such recognition can result in sterile inflammation and autoimmunity, including SLE (4, 15, 16). The connection of the endosomal TLRs with SLE originates mainly from mouse models, where TLR7 signaling seems to play a central role. TLR7 gene duplication is the cause for the development of lupus in mice bearing the Y chromosome-linked autoimmune accelerating (Yaa) locus that harbors 17 genes, including TLR7 (17, 18). In TLR7 transgenic mouse lines, a modest increase in TLR7 expression promotes autoreactive lymphocytes with RNA specificities and myeloid cell proliferation, but a substantial increase in TLR7 expression causes fatal acute inflammatory pathology and profound dendritic cell (DC) dysregulation (17). In addition, studies in several lupus-prone mouse strains have revealed that TLR7-deficiency ameliorates disease, but TLR9-deficiency exacerbates it. Interestingly, this controversy can be explained by the enhanced TLR7 activity in the TLR9-deficient lupus mice (19, 20). Although murine TLR8 does not seem so far to be able to sense a ligand (21, 22), we have shown previously that it plays an important biological role in controlling TLR7-mediated lupus. Indeed, TLR8-deficiency in mice (on the C57BL/6 background that is not prone to lupus) leads to lupus development because of increased TLR7 expression and signaling in DCs (23). Thus, tight control and regulation of TLR7 is pivotal for avoiding SLE and inflammatory pathology in mice. Recent studies in humans have also revealed that increased expression of TLR7 is associated with increased risk for SLE (24–26).Nucleic acid TLRs are expressed in many cell types, including DCs, plasmacytoid DCs (pDCs) and B cells, all of which play a central role in SLE development. TLR7, TLR8, and TLR9 signal through the adaptor molecule myeloid differentiation primary response gene 88 (MyD88), whereas TLR3 signals via the adaptor TRIF (Toll/IL-1 receptor domain-containing adaptor inducing IFN-β) (5). MyD88-deficiency abrogates most attributes of lupus in several lupus-prone mouse strains (19, 27–29). Moreover, deficiency for Unc93B1, a multipass transmembrane protein that controls trafficking of TLRs from the endoplasmic reticulum to endolysosomes and is required for nucleic acid-sensing TLR function (30), also abrogates many clinical parameters of disease in mouse lupus strains, suggesting that endosomal TLRs are critical in this disease (31). Interestingly, TLR9 competes with TLR7 for Unc93B1-dependent trafficking and predominates over TLR7 (32). TLR9 predominance is reversed to TLR7 by a D34A mutation in Unc93B1 and mice that carry this mutation show TLR7-dependent, systemic lethal inflammation (32).Thus, in mice both TLR8 and TLR9 control TLR7-mediated lupus, but it is unknown if these TLRs act in parallel or in series in the same or different cell types and if they have an additive effect or not in controlling TLR7. To address these issues, we generated double TLR8/TLR9-deficient (TLR8/9−/−) mice and analyzed and compared the lupus phenotype in TLR8−/−, TLR9−/−, and TLR8/9−/− mice. Our data revealed that TLR8/9−/− mice have increased abnormalities characteristic of SLE and that both TLR8 and TLR9 keep TLR7-mediated lupus under control, but they act in different cell types. On DCs TLR7 function is ruled by TLR8, whereas on B cells TLR7 is mastered by TLR9. 相似文献
70.
Christiane Mariotini-Moura Matheus Silva e Bastos Felipe Freitas de Castro Mellina Lanna Trindade Raphael de Souza Vasconcellos Myrian Augusta Araújo Neves-do-Valle Bernardo Pereira Moreira Ramon de Freitas Santos Claudia Miranda de Oliveira Luana Celina Seraphim Cunha Xênia Macedo Souto Gustavo Costa Bressan Abelardo Silva-Júnior Munira Muhammad Abdel Baqui Maria Terezinha Bahia Márcia Rogéria de Almeida José Roberto Meyer-Fernandes Juliana Lopes Rangel Fietto 《Acta tropica》2014
Previous work has suggested that Trypanosoma cruzi diphosphohydrolase 1 (TcNTPDase-1) may be involved in the infection of mammalian cells and serve as a potential target for rational drug design. In this work, we produced recombinant TcNTPDase-1 and evaluated its nucleotidase activity, cellular localization and role in parasite adhesion to mammalian host cells. TcNTPDase-1 was able to utilize a broad range of triphosphate and diphosphate nucleosides. The enzyme's Km for ATP (0.096 mM) suggested a capability to influence the host's ATP-dependent purinergic signaling. The use of specific polyclonal antibodies allowed us to confirm the presence of TcNTPDase-1 at the surface of parasites by confocal and electron microscopy. In addition, electron microscopy revealed that TcNTPDase-1 was also found in the flagellum, flagellum insertion region, kinetoplast, nucleus and intracellular vesicles. The presence of this enzyme in the flagellum insertion region and vesicles suggests that it may have a role in nutrient acquisition, and the widespread distribution of TcNTPDase-1 within the parasite suggests that it may be involved in other biological process. Adhesion assays using anti-TcNTPDase-1 polyclonal antibodies as a blocker or purified recombinant TcNTPDase-1 as a competitor revealed that the enzyme has a role in parasite–host cell adhesion. These data open new frontiers to future studies on this specific parasite–host interaction and other unknown functions of TcNTPDase-1 related to its ubiquitous localization. 相似文献