全文获取类型
收费全文 | 80461篇 |
免费 | 6061篇 |
国内免费 | 3604篇 |
专业分类
耳鼻咽喉 | 347篇 |
儿科学 | 1469篇 |
妇产科学 | 846篇 |
基础医学 | 12837篇 |
口腔科学 | 1663篇 |
临床医学 | 6787篇 |
内科学 | 13937篇 |
皮肤病学 | 1023篇 |
神经病学 | 7513篇 |
特种医学 | 1303篇 |
外国民族医学 | 15篇 |
外科学 | 4762篇 |
综合类 | 13861篇 |
现状与发展 | 22篇 |
预防医学 | 4568篇 |
眼科学 | 950篇 |
药学 | 10412篇 |
9篇 | |
中国医学 | 2558篇 |
肿瘤学 | 5244篇 |
出版年
2024年 | 55篇 |
2023年 | 824篇 |
2022年 | 1468篇 |
2021年 | 2736篇 |
2020年 | 2380篇 |
2019年 | 2045篇 |
2018年 | 2015篇 |
2017年 | 2331篇 |
2016年 | 2655篇 |
2015年 | 3002篇 |
2014年 | 5056篇 |
2013年 | 5660篇 |
2012年 | 5363篇 |
2011年 | 5988篇 |
2010年 | 4743篇 |
2009年 | 4601篇 |
2008年 | 4735篇 |
2007年 | 4594篇 |
2006年 | 4122篇 |
2005年 | 3877篇 |
2004年 | 3172篇 |
2003年 | 2702篇 |
2002年 | 2068篇 |
2001年 | 1777篇 |
2000年 | 1532篇 |
1999年 | 1267篇 |
1998年 | 1105篇 |
1997年 | 945篇 |
1996年 | 793篇 |
1995年 | 728篇 |
1994年 | 699篇 |
1993年 | 585篇 |
1992年 | 505篇 |
1991年 | 473篇 |
1990年 | 394篇 |
1989年 | 310篇 |
1988年 | 295篇 |
1987年 | 286篇 |
1986年 | 255篇 |
1985年 | 361篇 |
1984年 | 317篇 |
1983年 | 210篇 |
1982年 | 244篇 |
1981年 | 191篇 |
1980年 | 164篇 |
1979年 | 109篇 |
1978年 | 91篇 |
1977年 | 77篇 |
1976年 | 67篇 |
1975年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 234 毫秒
61.
62.
《The Journal of arthroplasty》2021,36(9):3118-3122
BackgroundThis study aimed to assess the baseline levels of D-dimer, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) and monitor the natural course of these serum markers after uneventful primary total joint arthroplasty.MethodsThis prospective study enrolled 81 patients undergoing primary total knee arthroplasty or total hip arthroplasty. The level of serum D-dimer, CRP, and ESR was measured preoperatively and on postoperative days 1, 3, 5, 15, and 45. Mean peak values, peak times, and distribution were compared between D-Dimer, CRP, and ESR.ResultsThe mean preoperative serum D-dimer, CRP, and ESR level was 412 ± 260 (range 200-980) ng/mL, 2.93 ± 2.1 (range 1-18) mg/L, and 22.88 ± 17.5 (range 3-102) mm/h, respectively. The highest mean peak for D-dimer, CRP, and ESR was at postoperative day 1, 3, and 5, respectively.ConclusionD-dimer levels reached peak levels on postoperative day 1 and then declined rapidly to a plateau level by postoperative day 3. A second, albeit small, peak in the level of D-dimer occurred on postoperative day 15. The level of CRP and ESR remained elevated for much longer with CRP returning to baseline on postoperative day 45 and the level of ESR had not returned back to normal on postoperative day 45. 相似文献
63.
Meng Ye Xiang-Jiang Guo Ke-Jia Kan Qi-Hong Ni Jia-Quan Chen Han Wang Xin Qian Guan-Hua Xue Hao-Yu Deng Lan Zhang 《中华医学杂志(英文版)》2021,134(1):73
Background:Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment. 相似文献
64.
Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
Background
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.Objectives
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.Methods
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.Results
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.Conclusions
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study. 相似文献65.
Type 2 diabetes mellitus (T2DM) is a complicated metabolic disease and has become one of the significant medical problems worldwide. Researchers aim to provide fine-tuned treatment for T2DM with minimal exposed side effects. Nutraceuticals are compounds or materials and emerging evidence suggests that the use of nutraceuticals has recently been recognized as a promising option for the prevention and management of T2DM, such as probiotics and prebiotics, Vitamin D, n-3 long-chain polyunsaturated fatty acids, and Plant-derived nutraceuticals. This review attempts to show the most popular nutraceuticals and review their effects and possible mechanisms in the prevention or glycemic control of T2DM. 相似文献
66.
Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
67.
68.
Cutaneous histiocytoses constitute a heterogeneous group of diseases characterised by the cutaneous accumulation of cells with the cytological and phenotypic features of macrophages or dendritic cells. The clinical spectrum ranges from self-resolving, skin-limited conditions to severe, multiorgan disease with a high morbidity rate. Until recently, cutaneous histiocytoses were classified according to the immunophenotype of the pathological cells, with differentiation between Langerhans cell histiocytosis (LCH) [CD1a+, CD207 (langerin)+] and non-Langerhans cell histiocytosis (CD68+, CD163+, CD1a?, CD207?). Over the last 12 years, a number of new pathophysiological findings (in particular, molecular pathology results) regarding histiocytoses have contributed to a new classification based on molecular alterations, as well as on clinical and imaging characteristics and the phenotype. The most frequent entities in children are juvenile xanthogranuloma and LCH. 相似文献
69.
Gerard A. Tarulli Samuel M. Cripps Andrew J. Pask Marilyn B. Renfree 《Developmental dynamics》2022,251(4):609-624
The formation of the external genitalia is a highly complex developmental process, considering it involves a wide range of cell types and results in sexually dimorphic outcomes. Development is controlled by several secreted signalling factors produced in complex spatiotemporal patterns, including the hedgehog (HH), bone morphogenic protein (BMP), fibroblast growth factor (FGF) and WNT signalling families. Many of these factors act on or are influenced by the actions of the androgen receptor (AR) that is critical to masculinisation. This complexity of expression makes it difficult to conceptualise patterns of potential importance. Mapping expression during key stages of development is needed to develop a comprehensive model of how different cell types interact in formation of external genitalia, and the global regulatory networks at play. This is particularly true in light of the sensitivity of this process to environmental disruption during key stages of development. The goal of this review is to integrate all recent studies on gene expression in early penis development to create a comprehensive spatiotemporal map. This serves as a resource to aid in visualising potentially significant interactions involved in external genital development. 相似文献
70.
《Clinical breast cancer》2022,22(6):507-514
Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC. 相似文献