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Mariabeatrice Principi Richard Day Stefania Marangi Osvaldo Burattini Vincenzo De Francesco Marcello Ingrosso 《Immunopharmacology and immunotoxicology》2013,35(2):185-195
Tumor necrosis factor alpha (TNFα) in intestinal mucosa plays a key role in the inflammation characterizing Crohn’s disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFα and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFα and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFα and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFα in CD. In conclusion, TNFα and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFα. 相似文献
104.
Moisés Armides Franco-Molina Yareellys Ramos-Zayas Erika Evangelina Coronado-Cerda Edgar Mendoza-Gamboa Pablo Zapata-Benavides Silvia Elena Santana-Krymskaya 《Immunopharmacology and immunotoxicology》2013,35(5):437-443
AbstractObjective: The aim of the present study was to evaluate the therapeutic potential of autologous DCs loaded with whole tumor cell lysate of CTVT generated under a simplified and rapid procedure in vitro production process, in a vulvar submucosal model of CTVT in dogs.Materials and methods: We generated a model of intravulvar CTVT in dogs. A CTVT lysate antigen was prepared according to the method of 1-butanol and after administered with complete Freund's adjuvant via subcutaneous in female healthy dogs and challenge with CTVT cells to corroborate the immunogenicity. Short-time generated dendritic cell pulsed with CTVT whole-lysate was performed, and analyzed by FITC-dextran uptake assay and characterized using anti-canine monoclonal antibodies CD14, CD80, CD83, and DLAII by flow cytometry. Dendritic cell therapy was administered in a frequency of three times every 2 weeks when the CTVT had 4 months of growth and 89?±?5 cm diameter. The CD3+, CD4+ and CD8+ lymphocytes were determined by flow cytometry, and IFN-γ by ELISA assay.Results and discussion: The administration of CTVT whole-lysate resulted in tumor prevention. The short-time generated dendritic cell pulsed with CTVT whole-lysate administration resulted in an efficient reduction and elimination of CTVT, probably due to the increase in lymphocyte populations (CD3+, CD4+, and CD8+), IFN-γ production and tumor infiltrating lymphocytes.Conclusion: In conclusion, this study demonstrates the efficacy of immunotherapy based in short-time generated dendritic cell pulsed with CTVT whole-lysate for the treatment of CTVT, and offer veterinary oncologists new alternative therapies to treat this and another malignancy. 相似文献
105.
《Immunopharmacology and immunotoxicology》2013,35(4):656-662
Although researchers have recently begun to pay more attention to the immunological characteristics of microvascular endothelial cells (MVECs), there are no reports on whether activation of MVECs by interferon-γ (IFN-γ) exerts any influence on the expressions of IFN-α/β. In the present study, we examined the influence of IFN-γ on the expressions of IFN-α/β in rat intestinal mucous MVECs (RIMMVECs). Different concentrations of IFN-γ were used to stimulate cultured RIMMVECs in vitro, and the cells and cell supernatants were collected at different time intervals. The influence of IFN-γ on the expressions of IFN-α/β in the RIMMVECs was examined at the mRNA and protein levels by real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results indicated that IFN-γ was able to activate RIMMVECs, thereby leading to upregulated expressions of IFN-α/β. The real-time quantitative PCR analyses indicated that the IFN-α/β mRNA expression levels in RIMMVECs achieved their peak values after stimulation with IFN-γ at 20?ng/mL for 6?h and were increased by 14.88- and 3.82-fold, respectively, when compared with the levels in negative control cells. The ELISA analyses revealed that the IFN-α/β protein expression levels achieved their peak values after stimulation with IFN-γ at 40?ng/mL. The expression of IFN-α protein achieved its peak value at 12?h, while the expression of IFN-β protein achieved its peak value after 6?h. The present results suggest that the expression and secretion of IFNs may participate in the immunologic barrier function of MVECs. 相似文献
106.
Mioko Mori Tomohiro Kumada Kenji Inoue Fumihito Nozaki Katsuyuki Matsui Yoshihiro Maruo Mamiko Yamada Hisato Suzuki Kenjiro Kosaki Minoru Shibata 《Brain & development》2021,43(6):724-728
BackgroundThe MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients’ quality of life.CaseA 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient’s clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient’s refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death.ConclusionThe pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and β-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered. 相似文献
107.
Effective immune strategies for eradication of human malignancies will require a thorough understanding of the interactions of cancer with the immune system. It will be crucial to understand how to optimize and sustain a T cell immune response. Recently, our understanding of the molecular interaction that occurs between an APC and a T cell during cognate interaction has increased dramatically. In this review, various costimulatory and inhibitory molecules of the B7 and TNF families will be discussed. The emphasis will be on how these costimulatory molecules impact T cell activation and on how they can be potentially used for the treatment of cancer. costimulation cancer T cell activation 相似文献
108.
通过对束流匹配的加速器进行计划设计,比较计划参数,验证交叉执行的差异及通过率,验证束流匹配的可行性及可靠性。选取头颈、胸部和腹盆部共15例病例,分别设计Clinac iX和Trilogy两个不同治疗机的三维适形计划(3D-CRT);另选头颈、胸部和腹盆部共15例病例,分别设计两个不同治疗机的调强计划(IMRT)。比较相同计划类型不同治疗机的计划差异,评价指标包括靶区PTV的D98%、D2%、Dmax,晶体Dmax、脑干Dmax、左右肺V5 Gy、双肺V20 Gy、脊髓Dmax、膀胱D50%、小肠D2 cc、股骨头V40 Gy等危及器官及治疗机跳数MU。并对治疗机执行计划进行点剂量和面剂量验证。PTV的D98%、D2%、Dmax剂量差异最大平均值标准差分别为-0.52%±0.30%、0.53%±0.45%、-0.55%±0.17%,危及器官剂量差异最大平均值为膀胱D50%(0.94%±0.84%);Clinac iX和Trilogy治疗机执行所有计划的最大绝对剂量偏差分别为2.36%和-2.80%。MatriXX和PV的γ验证通过率结果平均值分别在97.00%和96.00%以上,Clinac iX最小值为95.40%,Trilogy最小值为95.90%。两台经过束流匹配的治疗机之间交换执行计划的剂量学偏差在临床可接受的范围内,各项参数能精准执行,必要时可以在两台治疗机之间交换执行计划,保证病人放疗疗程完整。 相似文献
109.
Yan Li Yuan-Yi Zhang Li-Teng Yang Jiang-Qi Liu Chuan Zhou Zhi-Qiang Liu Gui Yang Li-Hua Mo Zhi-Gang Liu Bai-Sui Feng Ping-Chang Yang 《European journal of immunology》2021,51(2):459-470
Ulcerative colitis (UC) is a disease that frequently relapses and affects more than 0.1% general population; the underlying mechanism is poorly understood. Published data show that polymorphonuclear neutrophils (PMN) contribute to the pathogenesis of UC. This study aims to identify antigen (Ag)-specific PMNs and investigate their role in UC relapse. In this study, the correlation between PMN activities and UC relapse was assessed in a group of UC patients. A UC mouse model was developed to expand the findings of UC patient study. The results showed that a positive correlation was detected between the high PMN activities and the food Ag-specific IgG amounts in colon biopsies of UC patients. UC patient-derived Ag-specific PMNs could be activated upon exposure to food specific Ag. The Ag/FcγRI complexes were detected on the surface of PMNs in UC patients. Re-exposure of sensitized PMNs to specific Ag triggered PMN activation and induced UC-like inflammation in the mouse colon. We conclude that FcγRI plays a critical role in UC relapse. Inhibition of FcγRI can efficiently inhibits experimental UC. 相似文献