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1.
Fabrice Barlesi Edward B. Garon Dong-Wan Kim Enriqueta Felip Ji-Youn Han Joo-Hang Kim Myung-Ju Ahn Mary Jo Fidler Matthew A. Gubens Gilberto de Castro Veerle Surmont Qiao Li Anne C. Deitz Gregory M. Lubiniecki Roy S. Herbst 《Journal of thoracic oncology》2019,14(5):793-801
Introduction
In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.Methods
Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.Results
Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.Conclusions
These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. 相似文献2.
3.
Carlotta Castagnoli Claudia Trombotto Sabzima Ondei Maurizio Stella Maurizio Calcagni Gilberto Magliacani Simone Teich Alasia 《Burns : journal of the International Society for Burn Injuries》1997,23(7-8):565-572
In this study, skin-infiltrating cells were characterized in both the active and remission phases of post-burn hypertrophic scar biopstes. Immunohistochemistry examination of active phase samples showed an abundant presence of Langerhans cells, T cells, macrophages, a low presence of natural killer cells and the lack of B lymphocytes. In active hypertrophic scars T lymphocytes infiltrate deep into the superficial dermis and are also observed in the epidermis: CD3+ cells were present at about 222±107 per 0.25 mm2. In particular the analysis of lymphocyte subpopulations showed that CD4+ T cells predominate in the dermis as well as in the epidermis of active hypertrophic scars whereas CD8+ cells were less well represented (CD4/CD8 ratio is 2.06). This distribution was also shown in remission phase samples and in normotrophic scar specimens, although the lymphocyte number was significantly lower. Approximately 70 per cent of T lymphocytes present in the tissue involved in active phase hypertrophic scar samples were activated (positive with anti-HLA-DR and IL-2 receptor antibodies) which is significantly higher than remission phase hypertrophic and normotrophic scars, in which positivity was 40 and 38 per cent, respectively. Upon activation, the lesional lymphocytes release several cytokines, locally and transiently, that interact with specific receptors in response to different stimulation. Central to the immune hypothesis of hypertrophic scars is that some of the T-cell lymphokines act on keratinocytes, fibroblasts and other cell types to induce changes characteristic of these scars. The presence and close proximity of activated T lymphocytes and antigen-presenting cells of various phenotypes in both the epidermis and dermis of hypertrophic tissues provides strong circumstantial evidence of a local immune response. However, the manner in which T cells achieve and maintain their activated state in hypertrophic tissues in not yet known, and both antigen-dependent and independent mechanisms may contribute. 相似文献
4.
Reducing the Occupational Risk of Infections for the Surgeon: Multicentric National Survey on More Than 15,000 Surgical Procedures 总被引:2,自引:0,他引:2
Andrea Pietrabissa Stefano Merigliano Marco Montorsi Gilberto Poggioli Marco Stella Domenico Borzomati Enrico Ciferri Giuseppe Rossi Gianbattista Doglietto 《World journal of surgery》1997,21(6):573-578
The objective of this study was to find the incidence of accidental exposures to blood and body fluids among surgeons during operations and to describe their dynamics. A probabilistic model was also used to predict the cumulative 30-year risk to the surgeon of contracting hepatitis B and C viruses (HBV, HCV) or human immunodeficiency virus (HIV) infection and estimate the effect of preventive strategies in reducing this risk. A multicentric prospective survey, based on self-administered questionnaires, was conducted during a period of 6 months in 39 Italian hospitals. An accidental exposure to blood or body fluids occurred in 9.2% of 15,375 operations. In about 2% of procedures a parenteral-type injury, such as actual skin puncture or eye contamination, was suffered by the operating surgeon. A needle-stick injury was the commonest accident, and its occurrence was found to vary with the phase of the procedure and its length. The current lifetime risk of acquiring HBV, HCV, and HIV infection in our regions was estimated to be as high as 42.7%, 34.8%, and 0.54%, respectively. The adoption of preventive strategies is expected to reduce this risk to 21% for HBV, 16.6% for HCV, and 0.23% for HIV infection. Active immunization of surgeons against HBV is strongly recommended. The case is also made for the use of a face-shield combined with a permanent change in our surgical practice capable of reducing the current high rate of parenteral injuries. 相似文献
5.
Gilberto Goissis Sergio Akinobu Yoshioka Domingo Marcolino Braile & Vladimir Donizeti Aparecido Ramirez 《Artificial organs》1998,22(3):210-214
This work describes the results of the controlled crosslinking of collagen matrices by glutaraldehyde based on a double protection strategy, glutaraldehyde acetals and lysine protonation due to the acidic conditions of acetal formation. Materials crosslinked by this approach were characterized by thermal stability comparable to those obtained by conventional procedures with mechanical properties expected for bioprosthesis manufacture and with a higher stability toward collagenase hydrolysis. The integrity of the microfibrillar structure was confirmed by optical and scanning electronic microscopy. The results indicate that the glutaraldehyde acetals procedure may be of potential use for the crosslinking of bovine pericardium used in the manufacture of bioprosthetic devices. Advantages may be related to the production of materials with homogeneous crosslinking distributions, associated with better definition in the nature of the chemical link that they introduce, due to a better distribution of glutaraldehyde within the tissue matrix before the crosslinking reaction is allowed to occur. As a result, materials with improved biological and mechanical properties are expected. 相似文献
6.
Ictal chronology and interictal spikes predict perfusion patterns in temporal lobe epilepsy: a multivariate study. 总被引:2,自引:0,他引:2
Lauro Wichert-Ana Tonicarlo Rodrigues Velasco Vera Cristina Terra-Bustamante Veriano Alexandre Ricardo Guarnieri Roger Walz Mery Kato Whemberton Martins Araújo Carlos Gilberto Carlotti David Araújo Antonio Carlos Dos Santos Américo Ceiki Sakamoto 《Seizure》2004,13(5):346-357
Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive variables for the occurrence of TPP and APP. Fifty-one TLE patients were submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and multivariate (MVA) analysis were performed upon clinical data, distribution of interictal spikes, and ictal chronology of seizures. From MVA, a final predictive model (FPM) was determined to better predict TPP and APP. Forty patients showed TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P = 0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the electrographic seizure occurring after completion of tracer injection, and longer clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic-clonic seizures did not result in more APP. We concluded that analysis of ictal SPECT in TLE requires the knowledge of TPP and APP, the distribution of interictal spikes on temporal lobes and the ictal chronology of seizures. BIS showed that beyond a more complex epileptogenicity and seizure propagation, they may also lead to APP. 相似文献
7.
Emiri Tejima Bing-Qiao Zhao Kiyoshi Tsuji Anna Rosell Klaus van Leyen R Gilberto Gonzalez Joan Montaner Xiaoying Wang Eng H Lo 《Journal of cerebral blood flow and metabolism》2007,27(3):460-468
We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP-9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP-9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP-9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP-9 in blood, hemoglobin-induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema. 相似文献
8.
Georges Dellatolas Lucia Willadino Braga Ligia do Nascimento Souza Gilberto Nunes Filho Elizabeth Queiroz Gerard Deloche 《Journal of the International Neuropsychological Society》2003,9(5):771-782
The effect of the degree of illiteracy (complete or incomplete) on phonological skills, verbal and visual memory and visuospatial skills is examined in 97 normal Brazilian adults who considered themselves illiterate, and 41 Brazilian school children aged 7 to 8 years, either nonreaders or beginning readers. Similar literacy effects were observed in children and in adults. Tasks involving phonological awareness and visual recognition memory of nonsense figures distinguish the best nonreaders and beginning readers. Children performed better than adults at oral repetition of short items and figure recall, and adults better than children at semantic verbal fluency, digit span, and word list recall. A principal component analysis of the correlations between tasks showed that phonological awareness/reading, phonological memory/oral repetition, and semantic verbal memory/fluency tasks, generated different components. The respective role of culturally based preschool activities and literacy on the cognitive functions that are explored in this study is discussed. 相似文献
9.
Fernández M Fernández G Diez-Ewald M Torres E Vizcaíno G Fernández N Narváez J Arteaga-Vizcaíno M 《Investigación clínica》2005,46(2):187-195
The increase of plasmatic homocysteine (Hc) in pregnant women, who later develop preeclampsia/eclampsia, the cause of this increment and its pathogenic role in toxemia of pregnancy, are still controversial. The objectives of the present research were to determine the plasmatic He concentrations during the first and second trimesters of pregnancy and the effect of folic acid administration on these values, and in the prevention of preeclampsia. Ninety six pregnant women of low economic background were studied on the first prenatal consultation: 27 women in the first trimester of pregnancy and 59 in the second. After 8 hours of fasting, venous blood was extracted and each patient was provided with 1 mg folic acid tablets and instructed to ingest one tablet daily, and to come back to the laboratory after three months. Plasma homocysteine and serum folic acid were determined for each patient before and after the folic acid treatment, by using the IMX system (Abbott Lab) and radioimmunoassay, respectively. Basal homocysteine concentrations were 4.0 +/- 2.1 micromol/L and 4.8 +/- 2.1 micromol/L in the first and second trimesters respectively, with no significant modifications after three months of folic acid. Although the degree of desertion from the study was high, it was possible to determine the evolution of 65 pregnancies. Ten of them developed preeclampsia (15.4%). No significant differences were found in Hc concentrations, or the frequency of hyperhomocysteinemia in the different stages of pregnancy, between women with normal gestation and those who developed preeclampsia. The small sample size of these groups, preclude any valid conclusion, however the results do not suggest that Hc concentration or folic acid administration influence the development of toxemia of pregnancy. 相似文献
10.
Filaci G Contini P Fravega M Fenoglio D Azzarone B Julien-Giron M Fiocca R Boggio M Necchi V De Lerma Barbaro A Merlo A Rizzi M Ghio M Setti M Puppo F Zanetti M Indiveri F 《Human immunology》2003,64(1):9-20
Resident macrophages are mainly responsible for the clearance of apoptotic cells from tissue by phagocytosis. Phagocytosis of apoptotic cells is not accompanied by activation of inflammatory mechanisms, unlike what happens when necrotic phenomena occur. We analyzed the effect of phagocytosis of apoptotic bodies on macrophage cell functions. After phagocytosis of apoptotic cells macrophages were unable to present an exogenous antigen to autologous antigen-specific T-cell lines. The inhibition was mediated by different mechanisms including binding of apoptotic DNA to human leukocyte antigen (HLA) class II molecules of macrophages, decreased expression of co-stimulatory molecules and increased secretion of tumor growth factor beta (TGFbeta). When dendritic cells were cultured with macrophages phagocytosing apoptotic cells, or with their supernatant, impaired dendritic cell antigen presenting activity and reduced tumor necrosis factor alpha (TNFalpha) secretion were found. Our results suggest that: (1) the phagocytosis of apoptotic bodies inhibits macrophage antigen presentation; (2) such inhibition is mediated by the binding of apoptotic DNA to macrophage HLA class II molecules as well as by the activation of biological mechanisms that induce an anti-inflammatory functional behavior in macrophages; and (3) macrophages phagocytosing apoptotic cells inhibit antigen presentation of neighboring dendritic cells via TGFbeta secretion. These events are likely related to the preservation of healthy tissues from the onset of inflammation. 相似文献