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Background
Although positron emission tomography (PET) imaging is widely recommended in the evaluation of patients with lung cancer, randomized controlled trials (RCTs) assessing this have demonstrated inconsistent results. We asked whether differences in the clinical context and endpoints could explain these discrepancies.Methods
We used realist synthesis methods to analyze how contextual differences among RCTs affected the results. We focused on RCTs to minimize confounding yet permit evaluation of differences by comparing across studies.Results
This analysis suggests that the impact of PET depends on the clinical setting. PET is of greatest benefit in identifying M1 disease in patients with a high chance of such involvement and when little traditional imaging [e.g., abdominal/pelvis computed tomography (CT) and bone scan] is used. Identification of N2,3 involvement by PET prior to resection is seen primarily when there is at least a moderate probability of such and the rate of invasive staging is high. The rate of N2 disease not identified preoperatively appears to increase if PET is used to avoid invasive mediastinal staging in clinical settings in which the risk of N2,3 involvement is moderately high. There is both a potential benefit in avoiding stage-inappropriate resection as well as a risk of missed (stage-appropriate) resection if PET findings are not evaluated carefully.Conclusions
A blanket recommendation for PET may be too simplistic without considering nuances of the clinical setting. 相似文献93.
Garofalo A Giai C Lattar S Gardella N Mollerach M Kahl BC Becker K Prince AS Sordelli DO Gómez MI 《The Journal of infectious diseases》2012,206(1):81-90
Staphylococcus aureus protein A (SpA) plays a critical role in the induction of inflammation. This study was aimed to determine whether the number of short sequence repeats (SSRs) present in the polymorphic region modulates the inflammatory response induced by SpA. We demonstrated that there is a dose-response effect in the activation of interferon (IFN)-β signaling in airway epithelial and immune cells, depending on the number of SSRs, which leads to differences in neutrophil recruitment. We also determined that a significant proportion of isolates from patients with chronic infections such as osteomyelitis and cystic fibrosis carry fewer SSRs than do isolates from patients with acute infections or healthy carriers and that there was an inverse correlation between the number of SSRs and the length of disease course. Given the importance of IFN signaling in eradication of S. aureus, loss of SSRs may represent an advantageous mechanism to adapt to and persist in the host. 相似文献
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P Labarga P Barreiro A da Silva JM Guardiola R Rubio K Aguirrebengoa P Miralles J Portu MJ Téllez L Morano A Castro JA Pineda A Terrón J Hernández-Quero A Mariño MJ Ríos S Echeverría V Asensi E Vispo V Soriano;on behalf of PERICO Study Group 《The Journal of infectious diseases》2012,206(6):961-968
Background.?Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. Methods.?HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180?μg/d) plus either RBV standard dosing (1000 or 1200?mg/d if <75 or ≥75?kg, respectively) or RBV induction (2000?mg/d) along with subcutaneous erythropoietin β (450?IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. Results.?A total of 357 patients received ≥1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14?μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3?mg/dL; P?.005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P?=?.004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P?=?.007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P?=?.03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P?.001) as predictors of SVR. Conclusions.?A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV. 相似文献
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Juan V. Alegre-Requena Santiago Grijalvo Diego Sampedro Judith Mayr Csar Saldías Jos Juan Marrero-Tellado Ramn Eritja Raquel P. Herrera David Díaz Díaz 《RSC advances》2020,10(19):11481
(S)-2-Stearamidopentanedioic acid (C18-Glu) is a known LMW gelator that forms supramolecular gels in a variety of solvents. In this work, we have carried out the isosteric substitution of the amide group by a sulfonamide moiety yielding the new isosteric gelator (S)-2-(octadecylsulfonamido)pentanedioic acid (Sulfo-Glu). The gelation ability and the key properties of the corresponding gels were compared in terms of gelation concentration, gel-to-sol transition temperature, mechanical properties, morphology, and gelation kinetics in several organic solvents and water. This comparison was also extended to (S)-2-(4-hexadecyl-1H-1,2,3-triazol-4-yl)pentanedioic acid (Click-Glu), which also constitutes an isostere of C18-Glu. The stabilizing interactions were explored through computational calculations. In general, Sulfo-Glu enabled the formation of non-toxic gels at lower concentrations, faster, and with higher thermal-mechanical stabilities than those obtained with the other isosteres in most solvents. Furthermore, the amide-sulfonamide isosteric substitution also influenced the morphology of the gel networks as well as the release rate of an embedded antibiotic (vancomycin) leading to antibacterial activity in vitro against Staphylococcus aureus.Amide–sulfonamide isosteric substitution in a low-molecular-weight gelator enables fine-tuning of its gelation ability and the properties of the corresponding supramolecular gels. 相似文献