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1.
《Vaccine》2022,40(11):1594-1605
In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes. 相似文献
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Ahmed M. Abu El-Asrar Ajmal Ahmad Eef Allegaert Mohammad Mairaj Siddiquei Priscilla W. Gikandi Gert De Hertogh 《Ocular immunology and inflammation》2020,28(4):575-588
ABSTRACT
Purpose
To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163+ M2 macrophages in proliferative diabetic retinopathy (PDR). 相似文献4.
Purpose
Chest wall pain is an uncommon but bothersome late complication following lung stereotactic body radiation therapy. Despite numerous studies investigating predictors of chest wall pain, no clear consensus has been established for a chest wall constraint. The aim of our study was to investigate factors related to chest wall pain in a homogeneous group of patients treated at our institution.Patients and methods
All 122 patients were treated with the same stereotactic body radiation therapy regimen of 48 Gy in three fractions, seen for at least 6 months of follow-up, and planned with heterogeneity correction. Chest wall pain was scored according to the Common Terminology Criteria for Adverse Events classification v3.0. Patient (age, sex, diabetes, osteoporosis), tumour (planning target volume, volume of the overlapping region between planning target volume and chest wall) and chest wall dosimetric parameters (volumes receiving at least 30, 40, and 50 Gy, the minimal doses received by the highest irradiated 1, 2, and 5 cm3, and maximum dose) were collected. The correlation between chest wall pain (grade 2 or higher) and the different parameters was evaluated using univariate and multivariate logistic regression.Results
Median follow-up was 18 months (range: 6–56 months). Twelve patients out of 122 developed chest wall pain of any grade (seven with grade 1, three with grade 2 and two with grade 3 pain). In univariate analysis, only the volume receiving 30 Gy or more (P = 0.034) and the volume of the overlapping region between the planning target volume and chest wall (P = 0.038) significantly predicted chest wall pain, but these variables were later proved non-significant in multivariate regression.Conclusion
Our analysis could not find any correlation between the studied parameters and chest wall pain. Considering our present study and the wide range of differing results from the literature, a reasonable conclusion is that a constraint for chest wall pain is yet to be defined. 相似文献5.
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Selcen Yuksel Selim Ayhan Vugar Nabiyev Montse Domingo-Sabat Alba Vila-Casademunt Ibrahim Obeid Francisco Sanchez Perez-Grueso Emre Acaroglu 《The spine journal》2019,19(1):71-78
BACKGROUND CONTEXT
Health-related quality of life (HRQOL) parameters have been shown to be reliable and valid in patients with adult spinal deformity (ASD). Minimum clinically important difference (MCID) has become increasingly important to clinicians in evaluating patients with a threshold of improvement that is clinically relevant.PURPOSE
To calculate MCID and minimum detectable change (MDC) values of total scores of the Core Outcome Measures Index (COMI), Oswestry Disability Index (ODI), Physical Component Summary (PCS), Mental Component Summary (MCS) of the Short Form 36 (SF-36), and Scoliosis Research Society 22R (SRS-22R) in surgically and nonsurgically treated ASD patients who have completed an anchor question at pretreatment and 1-year follow-up.STUDY DESIGN/SETTING
Prospective cohort.PATIENT SAMPLE
Surgical and nonsurgical patients from a multicenter ASD database.OUTCOME MEASURES
Self-reported HRQOL measures (COMI, ODI, SF-36, SRS-22R, and anchor question).METHODS
A total of 185 surgical and 86 nonsurgical patients from a multicenter ASD database who completed pretreatment and 1-year follow-up HRQOL scales and the anchor question at the first year follow-up were included. The anchor question was used to determine MCID for each HRQOL measure. MCIDs were calculated by an anchor-based method using latent class analysis (LCA) and MDCs by a distribution-based method.RESULTS
All differences between means of baseline and first year postoperative total score measures for all scales demonstrated statistically significant improvements in the overall population as well as the surgically treated patients but not in the nonsurgical group. The calculated MDC and MCID values of HRQOL parameters in the entire study population were 1.34 and 2.62 for COMI, 10.65 and 14.31 for ODI, 6.09 and 7.33 for SF-36 PCS, 6.14 and 4.37 for SF-36 MCS, and 0.42 and 0.71 for SRS-22R. The calculated MCID values for surgical and non-surgical treatment groups were 2.76 versus 1.20 for COMI, 14.96 versus 2.45 for ODI, 7.83 versus 2.15 for SF-36 PCS, 5.14 versus 2.03 for SF-36 MCS, and 0.94 versus 0.11 for SRS-22R; the MDC values for surgical and nonsurgical treatment groups were 1.22 versus 1.51 for COMI, 10.27 versus 9.45 for ODI, 5.16 versus 6.77 for SF-36 PCS, 6.05 versus 5.67 for SF-36 MCS, and 0.38 versus 0.43 for SRS-22R.CONCLUSIONS
This study has demonstrated that MCID calculations for the HRQOL scales in ASD using LCA yield values comparable to other studies that had used different methodologies. The most important finding was the significantly different MCIDs for COMI, ODI, SF-36 PCS and SRS-22 in the surgically and nonsurgically treated cohorts. This finding suggests that a universal MCID value, inherent to a specific HRQOL for an entire cohort of ASD may not exist. Use of different MCIDs for surgical and nonsurgical patients may be warranted. 相似文献9.
Roberto V.P. Ribeiro Mitesh V. Badiwala Danny Ramzy Laura C. Tumiati Vivek Rao 《The Journal of thoracic and cardiovascular surgery》2019,157(2):615-625.e1
Objective
Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.Methods
Heart transplants were performed after 6 hours of cold ischemic storage. Recipient pigs were randomized to treatment with or without HTS (7.5% NaCl) before cardiopulmonary bypass (CPB). Using a myograft apparatus, coronary artery endothelial-dependent (Edep) and -independent (Eind) relaxation was assessed. LV performance was determined using pressure-volume loop analysis. Pulmonary interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α expression was measured.Results
Weaning from CPB and LV performance after transplantation were improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS-treated hearts (8 of 8 vs 2 of 8; P < .05). Mean LV functional recovery was improved in the HTS-treated animals, as assessed by preload recruitable stroke work (65 ± 10% vs 27 ± 10%; P < .001) and end-systolic elastance (55 ± 7% vs 37 ± 4%; P < .001). Treatment with HTS resulted in improved Edep (mean maximum elastance [Emax], 56 ± 5% vs 37 ± 7%; P < .001) and Eind (mean Emax%, 77 ± 6% vs 52 ± 4%; P < .001) vasorelaxation compared with control. Pulmonary expression of IL-2, IL-6, and TNF-α increased following transplantation, whereas HTS therapy attenuated IL production (P < .001). Transplantation increased plasma TNF-α levels and LV TNF-α expression, whereas HTS prevented this up-regulation (P < .001).Conclusions
Recipient HTS pretreatment preserves allograft vasomotor and LV function, and HTS therapy limits CPB-induced injury. HTS may be a novel recipient intervention to prevent graft dysfunction. 相似文献10.
A. Guerrero Gómez N. González Jaramillo J.A. Castro Pérez 《Revista espa?ola de anestesiología y reanimación》2019,66(1):10-17