全文获取类型
收费全文 | 9314篇 |
免费 | 823篇 |
国内免费 | 1244篇 |
出版年
2024年 | 15篇 |
2023年 | 125篇 |
2022年 | 278篇 |
2021年 | 448篇 |
2020年 | 334篇 |
2019年 | 468篇 |
2018年 | 391篇 |
2017年 | 294篇 |
2016年 | 396篇 |
2015年 | 578篇 |
2014年 | 705篇 |
2013年 | 720篇 |
2012年 | 908篇 |
2011年 | 923篇 |
2010年 | 551篇 |
2009年 | 459篇 |
2008年 | 535篇 |
2007年 | 491篇 |
2006年 | 456篇 |
2005年 | 347篇 |
2004年 | 309篇 |
2003年 | 284篇 |
2002年 | 237篇 |
2001年 | 174篇 |
2000年 | 131篇 |
1999年 | 128篇 |
1998年 | 103篇 |
1997年 | 88篇 |
1996年 | 81篇 |
1995年 | 45篇 |
1994年 | 67篇 |
1993年 | 33篇 |
1992年 | 47篇 |
1991年 | 33篇 |
1990年 | 23篇 |
1989年 | 18篇 |
1988年 | 17篇 |
1987年 | 26篇 |
1986年 | 12篇 |
1985年 | 21篇 |
1984年 | 5篇 |
1980年 | 7篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 7篇 |
1973年 | 6篇 |
1972年 | 8篇 |
1971年 | 9篇 |
1970年 | 4篇 |
1967年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 687 毫秒
141.
家蝇Phormicin作为防御素家族的成员,是一类具有广普抗菌活性的抗菌肽.本研究采用原核表达法表达并纯化获得了家蝇PhormicinA蛋白.将家蝇Phormicin A原核表达蛋白与完全佐剂和不完全佐剂乳化混匀,先后免疫新西兰白兔获得其多克隆抗体.通过原核表达蛋白中和吸附实验,以及Western blot实验验证了抗体的特异性.进一步用金黄色葡萄球菌刺激家蝇三龄幼虫样品,进行内源性验证并测定抗体的效价.结果 显示,该多克隆抗体既可以识别家蝇Phormicin A原核表达蛋白,也可以识别金黄色葡萄球菌刺激家蝇三龄幼虫产生的内源性Phormicin A蛋白.本研究为进一步探索Phormicin在家蝇天然免疫和防御中的机制等后续工作打下基础. 相似文献
142.
Wang Chaojie Gong Yandong Wei Anbang Huang Tao Hou Siyuan Du Junjie Li Zongcheng Wang Junliang Liu Bing Lan Yu 《中国科学:生命科学英文版》2021,64(12):2073-2087
Science China Life Sciences - During embryogenesis, hematopoietic stem progenitor cells (HSPCs) are believed to be derived from hemogenic endothelial cells (HECs). Moreover, arterial feature is... 相似文献
143.
144.
145.
146.
147.
Xiaolei Chen Yue Wang Ning Qu Bing Zhang Chun Xia 《Journal of cellular and molecular medicine》2021,25(3):1531-1545
Previous studies identified the involvement of phosphoinositide-specific phospholipase C (PLC) γ1 in some events of chondrocytes. This study aims to investigate whether and how PLCγ1 modulates autophagy to execute its role in osteoarthritis (OA) progression. Rat normal or human OA chondrocytes were pretreated with IL-1β for mimicking or sustaining OA pathological condition. Using Western blotting, immunoprecipitation, qPCR, immunofluorescence and Dimethylmethylene blue assays, and ELISA and transmission electron microscope techniques, we found that PLCγ1 inhibitor U73122 enhanced Collagen II, Aggrecan and GAG levels, accompanied with increased LC3B-II/I ratio and decreased P62 expression level, whereas autophagy inhibitor Chloroquine partially diminished its effect. Meanwhile, U73122 dissociated Beclin1 from Beclin1-IP3R-Bcl-2 complex and blocked mTOR/ULK1 axis, in which the crosstalk between PLCγ1, AMPK, Erk and Akt were involved. Additionally, by haematoxylin and eosin, Safranin O/Fast green, and immunohistochemistry staining, we observed that intra-articular injection of Ad-shPLCγ1-1/2 significantly enhanced Collagen and Aggrecan levels, accompanied with increased LC3B and decreased P62 levels in a rat OA model induced by anterior cruciate ligament transection and medial meniscus resection. Consequently, PLCγ1 inhibition-driven autophagy conferred cartilage protection against OA through promoting ECM synthesis in OA chondrocytes in vivo and in vitro, involving the crosstalk between PLCγ1, AMPK, Erk and Akt. 相似文献
148.
Bing Su Lijuan Zhang Wenfang Zhuang Wei Zhang Xiaofan Chen 《Journal of cellular and molecular medicine》2021,25(3):1546-1553
Although primary androgen deprivation therapy resulted in tumour regression, unfortunately, majority of prostate cancer progress to a lethal castration-resistant prostate cancer, finally die to metastasis. The mutual feedback between AKT and AR pathways plays a vital role in the progression and metastasis of prostate cancer. Therefore, the treatment of a single factor will eventually inevitably lead to failure. Therefore, better understanding of the molecular mechanisms underlying metastasis is critical to the development of new and more effective therapeutic agents. In this study, we created prostate cancer CWR22rv1 cells with the double knockout of Akt1 and Akt2 genes through CRISPR/Cas9 method to investigate the effect of Akt in metastasis of prostate cancer. It was found that knockout of Akt1/2 resulted in markedly reduced metastasis in vitro and in vivo, and appeared to interfere AR nuclear translocation through regulating downstream regulatory factor, FOXO proteins. It suggests that some downstream regulatory factors in the AKT and AR interaction network play a vital role in prostate cancer metastasis and are potential targeting molecules for prostate cancer metastasis treatment. 相似文献
149.
Ning Xie Yunfan Bai Lu Qiao Yuru Bai Jian Wu Yan Li Mingzuo Jiang Bing Xu Zhen Ni Ting Yuan Yongquan Shi Kaichun Wu Feng Xu Jinhai Wang Lei Dong Na Liu 《Journal of cellular and molecular medicine》2021,25(8):4014-4027
The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients. 相似文献
150.
Wei Liu Chunyu Wang Shengli Wang Kai Zeng Shan Wei Ning Sun Ge Sun Manlin Wang Renlong Zou Wensu Liu Lin Lin Huijuan Song Zining Jin Yue Zhao 《International journal of biological sciences》2021,17(1):188
Androgen receptor (AR) and its variants play vital roles in development and progression of prostate cancer. To clarify the mechanisms involved in the enhancement of their actions would be crucial for understanding the process in prostate cancer and castration-resistant prostate cancer transformation. Here, we provided the evidence to show that pre-mRNA processing factor 6 (PRPF6) acts as a key regulator for action of both AR full length (AR-FL) and AR variant 7 (AR-V7), thereby participating in the enhancement of AR-FL and AR-V7-induced transactivation in prostate cancer. In addition, PRPF6 is recruited to cis-regulatory elements in AR target genes and associates with JMJD1A to enhance AR-induced transactivation. PRPF6 also promotes expression of AR-FL and AR-V7. Moreover, PRPF6 depletion reduces tumor growth in prostate cancer-derived cell lines and results in significant suppression of xenograft tumors even under castration condition in mouse model. Furthermore, PRPF6 is obviously highly expressed in human prostate cancer samples. Collectively, our results suggest PRPF6 is involved in enhancement of oncogenic AR signaling, which support a previously unknown role of PRPF6 during progression of prostate cancer and castration-resistant prostate cancers. 相似文献