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991.
Ming Li Ling Wang Dian-Chun Shi Jia-Nee Foo Zhong Zhong Chiea-Chuen Khor Chiara Lanzani Lorena Citterio Erika Salvi Pei-Ran Yin Jin-Xin Bei Li Wang Yun-Hua Liao Jian Chen Qin-Kai Chen Gang Xu Geng-Ru Jiang Jian-Xin Wan Meng-Hua Chen Nan Chen Hong Zhang Yi-Xin Zeng Zhi-Hong Liu Jian-Jun Liu Xue-Qing Yu 《Journal of the American Society of Nephrology : JASN》2020,31(12):2949
992.
Ariela L. Marshall Renee K. Dversdal Martina Murphy Donna M. Prill Tian Zhang Shikha Jain 《Medical teacher》2020,42(2):228-230
AbstractMentorship is essential for career development, personal development, and job satisfaction for physicians in academic medicine. Women in academic medicine face unique challenges including significant gender disparities in positions of leadership as well as difficulty finding mentors. As leaders in academic medicine, we have collated several structured recommendations for physicians of both genders seeking to be better mentors to female trainees and early career physicians. We discuss each of these recommendations in detail including the following: acknowledging your own strengths and limitations as a mentor, addressing issues of work-life integration, helping your mentee set long-term career goals, and acting as a sponsor as well as a mentor. We hope these suggestions are helpful for current and aspiring mentors and provide a platform to improve career development for female physicians and reduce gender inequities in academic medicine. 相似文献
993.
Li-Mei Wang Xiao-Meng Chen Hai-Jing Yan Shu Yan Xiao-Yan Sun Da-Wei Zhang Hua Yang Dan-Li Lu Cheng-Ye Che 《国际眼科》2022,15(4):541-546
AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1 (CCPG1) is involved in the corneal antifungal immune response.
METHODS: Human corneal epithelial cells (HCECs) and human myeloid leukemia mononuclear cells (THP-1) macrophages stimulated by Aspergillus fumigatus (A. fumigatus) were used as cell models. The expression of CCPG1 mRNA was detected by qRT-PCR. Western blot was used to determine the protein expression of CCPG1 and interleukin-1β (IL-1β). The dectin-1 neutralizing antibody was used to detect the association between dectin-1 and CCPG1. Immunofluorescence was used to observe the colocalization of CCPG1 and C-type lectin-like receptor-1 (CLEC-1) in THP-1 macrophages.
RESULTS: The expression of CCPG1 started to increase at 4h after infection and increased in a time-dependent manner in HCECs and THP-1 macrophages. With dectin-1 neutralizing antibody pretreatment, the expression of IL-1β was down-regulated. CCPG1 up-regulation in response to A. fumigatus infection was independent of dectin-1. Immunofluorescence showed the colocalization of CCPG1 and CLEC-1 in THP-1 macrophages.
CONCLUSION: As a specific autophagy protein of non-canonical autophagy pathway, CCPG1 is involved in corneal infection with A. fumigatus. 相似文献
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Qiang Fu Le Xu Yiwei Wang Qi Jiang Zheng Liu Junyu Zhang Quan Zhou Han Zeng Shanyou Tong Tao Wang Yangyang Qi Baoying Hu Hangcheng Fu Huyang Xie Lin Zhou Yuan Chang Yu Zhu Bo Dai Jiejie Xu 《European urology》2019,75(5):752-763
Background
Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.Objective
To seek a potential therapeutic target in glutamine-addicted ccRCC.Design, setting, and participants
Tumors from ccRCC patients from a Shanghai cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC tumors and murine tumor cells.Outcome measurements and statistical analysis
Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and cytokine concentrations were determined. Survival was compared between different subpopulations of patients using Kaplan-Meier and Cox regression analyses.Results and limitations
We found that in ccRCC, high interleukin (IL)-23 expression was significantly associated with poor survival in both TCGA (overall survival [OS] hazard ratio [HR] = 2.04, cancer-specific survival [CSS] HR = 2.95; all p < 0.001) and Shanghai (OS HR = 2.07, CSS HR = 3.92; all p < 0.001) cohorts. IL-23 blockade prolongs the survival of tumor-bearing mice, promotes T-cell cytotoxicity in in vitro cultures of human ccRCC tumors, and augments the therapeutic benefits of anti-PD-1 antibodies. Mechanistically, glutamine consumption by ccRCC tumor cells results in the local deprivation of extracellular glutamine, which induces IL-23 secretion by tumor-infiltrating macrophages via the activation of hypoxia-inducible factor 1α (HIF1α). IL-23 activates regulatory T-cell proliferation and promotes IL-10 and transforming growth factor β expression, thereby suppressing tumor cell killing by cytotoxic lymphocytes. The positive correlations between glutamine metabolism, IL-23 levels, and Treg responses are confirmed in both TCGA cohort and tumors from Shanghai ccRCC patients. Study limitations include the unclear impacts of glutamine deprivation and IL-23 on other immune cells.Conclusions
Macrophage-secreted IL-23 enhanced Treg functions in glutamine-addicted tumors; thus, IL-23 is a promising target for immunotherapy in ccRCC.Patient summary
In this study, we analyzed the immune components in glutamine-addicted clear cell renal cell carcinoma (ccRCC) tumors from two patient cohorts and conducted both in vitro and in vivo studies. We found that ccRCC tumor cell-intrinsic glutamine metabolism orchestrates immune evasion via interleukin (IL)-23, and IL-23–high patients had significantly poorer survival than IL-23–low patients. IL-23 should thus be considered a therapeutic target in ccRCC, either alone or in combination with immune checkpoint inhibitors. 相似文献999.
Binghu Jiang Dongmei He Liwen Zhang Min Ye 《Journal of neuroradiology. Journal de neuroradiologie》2019,46(2):117-123
Background and purpose
It is not conclusive that magnetic resonance (MR)-based carotid atherosclerotic plaque assessment identifies high-risk features associated with cerebrovascular events. We aimed to systematically summarize the association of MR imaging (MRI)-determined intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and thinning/rupture of the fibrous cap (TRFC) with subsequent ischemic events.Materials and methods
We performed a comprehensive literature search evaluating the association of MRI-based carotid plaque composition with ischemic outcomes. We included cohort studies examining IPH, LRNC, or TRFC with mean follow-up of ≥ 6 months and an outcome measure of ipsilateral ischemic events. A meta-analysis was done according to the Cochrane guideline.Results
We identified 13 studies including 1.150 patients and 1.208 analyzed carotid arteries, with mean follow-up of 21.1 months. The hazard ratios (HR) for IPH, LRNC, and TRFC as predictors of subsequent ischemic events were 4.41 (95% CI: 2.87, 6.79), 3.00 (95% CI: 1.51, 5.95), and 5.94 (95% CI: 2.66, 13.28), respectively. The predictive value of carotid plaque MRI for ischemic events was acceptable, with sensitivity of 0.80 (95% CI: 0.66, 0.90) and specificity of 0.63 (95% CI: 0.57, 0.68). However, it was limited to confirm or exclude future ischemic events in clinical context, with positive likelihood ratio (LR) of 2.2 (95% CI: 1.9, 2.5) and negative LR of 0.31 (95% CI: 0.18, 0.55). No statistically significant heterogeneity or publication bias was observed.Conclusion
The presence of IPH, LRNC, and TRFC determined by MRI is associated with increased risk of future ischemic events, but its predictive value is moderate and should not be used for confirmation or exclusion of future ischemic events in clinical context. 相似文献1000.
Payam Sajedi Lydia Chelala Joel Nunez-Gonalez Carolyn Cronin Steven Kittner Jiachen Zhuo Yang Zhang Dheeraj Gandhi Prashant Raghavan 《Journal of neuroradiology. Journal de neuroradiologie》2019,46(2):136-140