全文获取类型
收费全文 | 14403篇 |
免费 | 962篇 |
国内免费 | 483篇 |
专业分类
耳鼻咽喉 | 55篇 |
儿科学 | 107篇 |
妇产科学 | 326篇 |
基础医学 | 2148篇 |
口腔科学 | 260篇 |
临床医学 | 927篇 |
内科学 | 1681篇 |
皮肤病学 | 153篇 |
神经病学 | 1149篇 |
特种医学 | 241篇 |
外国民族医学 | 13篇 |
外科学 | 1035篇 |
综合类 | 2231篇 |
预防医学 | 532篇 |
眼科学 | 421篇 |
药学 | 1402篇 |
2篇 | |
中国医学 | 849篇 |
肿瘤学 | 2316篇 |
出版年
2024年 | 16篇 |
2023年 | 145篇 |
2022年 | 306篇 |
2021年 | 283篇 |
2020年 | 222篇 |
2019年 | 286篇 |
2018年 | 345篇 |
2017年 | 337篇 |
2016年 | 371篇 |
2015年 | 389篇 |
2014年 | 736篇 |
2013年 | 925篇 |
2012年 | 849篇 |
2011年 | 1064篇 |
2010年 | 957篇 |
2009年 | 1007篇 |
2008年 | 1003篇 |
2007年 | 951篇 |
2006年 | 893篇 |
2005年 | 777篇 |
2004年 | 699篇 |
2003年 | 594篇 |
2002年 | 471篇 |
2001年 | 421篇 |
2000年 | 312篇 |
1999年 | 279篇 |
1998年 | 198篇 |
1997年 | 157篇 |
1996年 | 163篇 |
1995年 | 146篇 |
1994年 | 121篇 |
1993年 | 83篇 |
1992年 | 74篇 |
1991年 | 55篇 |
1990年 | 42篇 |
1989年 | 35篇 |
1988年 | 20篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 26篇 |
1984年 | 17篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 11篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
1.
《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
2.
3.
Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (Kd= 0.045nM) and low (Kd= 21nM) affinity125I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50–90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity. 相似文献
4.
Kamil Torres Anna Torres Grzegorz J. Staśkiewicz Andrzej Chrościcki Tadeusz Łoś Ryszard Maciejewski 《Surgical endoscopy》2009,23(9):2117-2123
Background Surgical procedures enhance production of pro- and anti-inflammatory cytokines and angiogenic factors that play a pivotal
role in the immunological response to surgical trauma and take part in the pathogenesis of tumor growth and adhesions formation.
The purpose of the study was to access the influence of low-pressure CO2 pneumoperitoneum on the inflammatory and angiogenic responses during the postoperative period after laparoscopy.
Methods The study group consisted of 40 patients, operated on due to cholelithiasis using standard-pressure (n = 20) and low-pressure (n = 20) CO2 pneumoperitoneum. Serum concentration of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF)-A, and
endostatin were measured before and at 6, 24, and 48 h after surgery with commercially available enzyme-linked immunosorbent
assay (ELISA).
Results Concentrations of IL-6 increased significantly after the operations in both groups. No differences were observed between the
groups in regards to IL-6, IL-8, and IL-10 levels. Concentrations of VEGF-A measured at 6 and 48 h were significantly lower
in patients who underwent laparoscopies performed with low-pressure pneumoperitoneum. No significant variations were observed
in endostatin serum concentration. Concentrations of the studied parameters were not influenced by duration of surgery or
by age, gender, or body mass index (BMI) of the patients.
Conclusions The results obtained in our study do not show any significant differences between studied operative procedures with regards
to systemic inflammatory response. Changes in the concentrations of VEGF-A and endostatin observed in the studied population
may suggest this technique is more favorable with regards to angiogenesis process intensity, along with all its consequences
and implications. 相似文献
5.
巨噬细胞移动抑制因子与鼻咽癌微血管生成和淋巴结转移的关系 总被引:9,自引:2,他引:7
[目的]研究巨噬细胞移动抑制因子(macrophage migration inhibitory factor,MIF)和血管内皮生长因子(vascular endothelial growth factor,VEGF)在鼻咽癌组织中的表达水平及其与肿瘤新生血管的关系,探讨细胞因子在鼻咽癌细胞侵袭转移过程中的作用.[方法]收集1999-2003年期间45例确诊未治的鼻咽原发癌活检组织标本,用LSAB免疫组化法检测鼻咽癌组织中MIF和VEGF表达,计数癌组织中新生血管热区的CD34阳性微血管密度(intratumoral microvessel density,IMD),并将各检测指标与患者的病理及临床资料相联系.[结果]鼻咽原发癌组织中,癌细胞MIF和VEGF的阳性表达率分别为78%(35/45)和71%(32/45),伴有淋巴结转移的癌组织中MIF和IMD水平均高于无淋巴结转移的癌组织,P=0.029,P=0.026,MIF阳性组的IMD计数为(35.1±13.3)/高倍视野,明显高于MIF阴性病例的(20.9±10.2)/高倍视野,P=0.003.以Schmincke型生长方式分布的癌细胞MIF表达水平(67.4%±35.2%)高于以Regaud型方式分布的癌细胞(32.9%±29.7%),P=0.007.癌细胞MIF与VEGF表达以及IMD计数均显示正相关关系,P<0.05.但癌细胞VEGF的表达与患者性别、年龄、病理组织学分型以及临床分期无统计学显著意义.[结论]MIF在鼻咽癌细胞的淋巴结转移过程中可能具有重要的促进作用,并可能是影响肿瘤性微血管生成和癌细胞VEGF表达的重要因素. 相似文献
6.
目的探讨血肿局部炎症、假膜新血管生成、局部纤溶状况及其在CSDH发生、发展中的作用。进而探讨CSDH的发病机制,并为CSDH的治疗及预防复发提供理论依据。方法以78例CSDH患者作为病例组,20例健康人作为正常对照组。采用ELISA法测定患者血清及血肿液中VEGF及IL-6的含量。比较患者末梢静脉血及血肿液中四种因子的含量变化并与正常对照组比较。结果病例组血肿液FDP、d-dimer检测均为阳性,血液为阴性;正常对照组血液FDP、d-dimer检测均为阴性;病例组血清VEGF含量与正常对照组比较差异无统计学意义。血肿液中VEGF浓度高于血清中。病例组血清IL-6浓度与正常对照组差异无统计学意义,血肿液中IL-6浓度高于血清中。CSDH患者血肿液VEGF、IL-6水平没有相关性。结论CSDH患者血肿液局部纤溶亢进,局部VEGF分泌旺盛,新血管生成活跃,局部炎症活跃,可导致CSDH不断扩大而参与CSDH发病机制。抗炎治疗、抑制VEGF的生理作用、有选择的对病人施行促凝治疗,可成为部分CSDH病人保守治疗及预防复发的有效手段。 相似文献
7.
8.
9.
Donna M. Ballantine Shelley A. Klemm Terry J. Tunny Michael Stowasser Richard D. Gordon 《Clinical and experimental pharmacology & physiology》1994,21(3):215-218
1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension. 相似文献
10.