全文获取类型
收费全文 | 6391篇 |
免费 | 733篇 |
国内免费 | 591篇 |
专业分类
7715篇 |
出版年
2024年 | 45篇 |
2023年 | 225篇 |
2022年 | 300篇 |
2021年 | 453篇 |
2020年 | 499篇 |
2019年 | 643篇 |
2018年 | 402篇 |
2017年 | 239篇 |
2016年 | 284篇 |
2015年 | 275篇 |
2014年 | 398篇 |
2013年 | 474篇 |
2012年 | 273篇 |
2011年 | 332篇 |
2010年 | 222篇 |
2009年 | 267篇 |
2008年 | 268篇 |
2007年 | 267篇 |
2006年 | 223篇 |
2005年 | 234篇 |
2004年 | 184篇 |
2003年 | 171篇 |
2002年 | 147篇 |
2001年 | 75篇 |
2000年 | 68篇 |
1999年 | 75篇 |
1998年 | 66篇 |
1997年 | 57篇 |
1996年 | 53篇 |
1995年 | 46篇 |
1994年 | 41篇 |
1993年 | 47篇 |
1992年 | 32篇 |
1991年 | 27篇 |
1990年 | 31篇 |
1989年 | 22篇 |
1988年 | 25篇 |
1987年 | 23篇 |
1986年 | 26篇 |
1985年 | 25篇 |
1984年 | 29篇 |
1983年 | 18篇 |
1982年 | 23篇 |
1981年 | 13篇 |
1980年 | 19篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1974年 | 6篇 |
排序方式: 共有7715条查询结果,搜索用时 15 毫秒
101.
Yueshui Zhao Sipeng Guo Jian Deng Jing Shen Fukuan Du Xu Wu Yu Chen Mingxing Li Meijuan Chen Xiaobing Li Wanping Li Li Gu Yuhong Sun Qinglian Wen Jing Li Zhangang Xiao 《International journal of biological sciences》2022,18(9):3845
Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC. 相似文献
102.
Mingshan Xue Teng Zhang Zhangkai J. Cheng Baojun Guo Yifeng Zeng Runpei Lin Peiyan Zheng Mingtao Liu Fengyu Hu Feng Li Wensheng Zhang Lu Li Qi Zhao Baoqing Sun Xiaoping Tang 《International journal of biological sciences》2022,18(12):4618
This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P<0.05) between patients and healthy controls (P<0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation. 相似文献
103.
Dai Sik Ko Junho Kang Hye Jin Heo Eun Kyoung Kim Kihun Kim Jin Mo Kang YunJae Jung Seung Eun Baek Yun Hak Kim 《International journal of biological sciences》2022,18(13):5154
Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (, GSE28829, GSE43292, and GSE100927), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro. Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 (PCK2) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2-KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis. GSE120521相似文献
104.
105.
【目的】研究乙酸合成途径阻断及NADH氧化酶表达对于谷氨酸棒杆菌生产乙偶姻的影响。【方法】在谷氨酸棒杆菌CGF2中异源表达als SD操纵子构建乙偶姻生产菌株CGT1,考察敲除乙酸生成途径cat和pqo对乙偶姻的影响。然后引入短乳杆菌的NADH氧化酶,在优化的溶氧条件下研究其对乙偶姻产量的影响。【结果】CGT1在摇瓶发酵中可积累6.27 g/L乙偶姻,敲除cat使乙偶姻产量显著提高30.94%,达到8.21 g/L;双敲除cat和pqo没有进一步提高产量。通过优化发酵的溶氧水平,乙偶姻产量达到10.06 g/L。在高溶氧水平下引入NADH氧化酶导致菌株的生长和糖代谢速率提高,但乙偶姻产量略有降低。在分批补料发酵中,重组菌株乙偶姻产量达到40.51 g/L,产率为0.51 g/(L?h)。【结论】在谷氨酸棒杆菌中阻断乙酸合成途径cat能够有效提高乙偶姻产量,NADH氧化酶在高溶氧水平下表达不利于乙偶姻的合成,需要进一步调节表达水平以确定其效果。 相似文献
106.
107.
108.
109.
110.