全文获取类型
收费全文 | 19341篇 |
免费 | 1421篇 |
国内免费 | 1280篇 |
出版年
2024年 | 42篇 |
2023年 | 265篇 |
2022年 | 562篇 |
2021年 | 957篇 |
2020年 | 584篇 |
2019年 | 825篇 |
2018年 | 825篇 |
2017年 | 583篇 |
2016年 | 857篇 |
2015年 | 1135篇 |
2014年 | 1381篇 |
2013年 | 1486篇 |
2012年 | 1717篇 |
2011年 | 1552篇 |
2010年 | 988篇 |
2009年 | 950篇 |
2008年 | 1059篇 |
2007年 | 991篇 |
2006年 | 808篇 |
2005年 | 685篇 |
2004年 | 535篇 |
2003年 | 520篇 |
2002年 | 439篇 |
2001年 | 345篇 |
2000年 | 299篇 |
1999年 | 295篇 |
1998年 | 166篇 |
1997年 | 158篇 |
1996年 | 157篇 |
1995年 | 119篇 |
1994年 | 84篇 |
1993年 | 70篇 |
1992年 | 110篇 |
1991年 | 82篇 |
1990年 | 68篇 |
1989年 | 52篇 |
1988年 | 43篇 |
1987年 | 43篇 |
1986年 | 38篇 |
1985年 | 51篇 |
1984年 | 8篇 |
1983年 | 17篇 |
1982年 | 9篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1974年 | 5篇 |
1969年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
871.
Qian Wei Lin Zhao Longyang Jiang Jia Bi Zhaojin Yu Lan Zhao Xinyue Song Mingli Sun Yuzong Chen Minjie Wei 《Journal of cellular physiology》2019,234(7):11888-11899
MiR-137 has been identified as potential hepatocellular carcinoma (HCC) prognostic biomarkers. Highly relevant HCC prognostic biomarkers may be derived from combinations of miR-137 with its target genes involved in the regulation of liver microenvironment. This study aimed at the discovery of such a combination with improved HCC prognosis performance than miR-137 or its target gene alone in a significantly higher number of HCC patients than previous studies. Analysis of the differentially expressed micro RNAs (miRNAs) between cancer and noncancer tissues reconfirmed miR-137 to be among the most relevant prognostic miRNAs and the data of 375 HCC patients and 50 normal cases were from the Cancer Genome Atlas (TCGA) data sets. Target genes were identified by the established search methods and Kaplan–Meier survival analysis of HCC patients was used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards regression indicated that the miR-137 and its target gene AFM combination is an independent prognostic factor for the OS and RFS in HCC. In vitro experiments validated that miR-137 could bind to 3′-untranslated region of the AFM and promote the invasion and metastasis of HCC cell lines. The expressions of miR-137 and its liver microenvironment regulatory target gene AFM in combination significantly correlated with HCC progression in a higher number of patients than in previous studies, which suggested their potential as prognostic biomarkers for HCC. 相似文献
872.
Qiushuang Ji Shuai Guo Xuzhao Wang Chunli Pang Yong Zhan Yafei Chen Hailong An 《Journal of cellular physiology》2019,234(6):7856-7873
TMEM16A (also known as anoctamin 1, ANO1) is the molecular basis of the calcium-activated chloride channels, with ten transmembrane segments. Recently, atomic structures of the transmembrane domains of mouse TMEM16A (mTMEM16A) were determined by single-particle electron cryomicroscopy. This gives us a solid ground to discuss the electrophysiological properties and functions of TMEM16A. TMEM16A is reported to be dually regulated by Ca2+ and voltage. In addition, the dysfunction of TMEM16A has been found to be involved in many diseases including cystic fibrosis, various cancers, hypertension, and gastrointestinal motility disorders. TMEM16A is overexpressed in many cancers, including gastrointestinal stromal tumors, gastric cancer, head and neck squamous cell carcinoma (HNSCC), colon cancer, pancreatic ductal adenocarcinoma, and esophageal cancer. Furthermore, overexpression of TMEM16A is related to the occurrence, proliferation, and migration of tumor cells. To date, several studies have shown that many natural compounds and synthetic compounds have regulatory effects on TMEM16A. These small molecule compounds might be novel drugs for the treatment of diseases caused by TMEM16A dysfunction in the future. In addition, recent studies have shown that TMEM16A plays different roles in different diseases through different signal transduction pathways. This review discusses the topology, electrophysiological properties, modulators and functions of TMEM16A in mediates nociception, gastrointestinal dysfunction, hypertension, and cancer and focuses on multiple regulatory mechanisms regarding TMEM16A. 相似文献
873.
Chengchuang Song Zhaoxin Yang Dong Dong Jiawei Xu Jian Wang Hui Li Yongzhen Huang Xianyong Lan Chuzhao Lei Yun Ma Hong Chen 《Journal of cellular physiology》2019,234(6):9839-9848
MicroRNAs (miRNAs) have been established to regulate skeletal muscle development in mammals. However, few studies have been conducted on the regulation of proliferation and differentiation of bovine myoblast cells by miRNAs. The aim of our study was to explore the function of miR-483 in cell proliferation and differentiation of bovine myoblast. Here, we found that miR-483 declined in both proliferation and differentiation stages of bovine myoblast cells. During the proliferation phase, the overexpression of miR-483 downregulated the cell cycle–associated genes cyclin-dependent kinase 2 (CDK2), proliferating cell nuclear antigen (PCNA) messenger RNA (mRNA), and the protein levels. At the cellular level, cell cycle, cell counting kit-8, and 5-ethynyl-2´-deoxyuridine results indicated that the overexpression of miR-483 block cell proliferation. During differentiation, the overexpression of miR-483 led to a decrease in the levels of the myogenic marker genes MyoD1 and MyoG mRNA and protein. Furthermore, the immunofluorescence analysis results showed that the number of MyHC-positive myotubes was reduced. In contrast, the opposite experimental results were obtained concerning both proliferation and differentiation after the inhibition of miR-483. Mechanistically, we demonstrated that miR-483 target insulin-like growth factor 1 (IGF1) and downregulated the expression of key proteins in the PI3K/AKT signaling pathway. Altogether, our findings indicate that miR-483 acts as a negative regulator of bovine myoblast cell proliferation and differentiation. 相似文献
874.
Guang-Cai Li Xu-Ling Qin Huai-Hua Song Ying-Ni Li Yu-Yan Qiu Shi-Chang Cui Yong-Sheng Wang Hui Wang Jun-Ling Gong 《Journal of cellular physiology》2019,234(12):22331-22342
Ovarian cancer characterizes as the fourth leading consequence of death associated with cancer for women. Accumulating evidence underscores the vital roles of microRNAs (miRNAs) in preventing ovarian cancer development. Besides, induction of the phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/Akt) pathway associated with the ovarian cancer cell migration and invasion. The study aims to examine the effects of miR-15b on the proliferation, apoptosis, and senescence of human ovarian cancer cells by binding to lysophosphatidic acid receptor 3 (LPAR3) with the involvement of the PI3K/Akt pathway. The positive expression of LPAR3 protein was detected by immunohistochemistry. Then the interaction between miR-15b and LPAR3 was examined. The possible role of miR-15b in ovarian cancer was explored using gain- and loss-of-function experiments. Subsequently, the functions of miR-15b on PI3K/Akt pathway, proliferation, migration, invasion, senescence and apoptosis of ovarian cancer cells were assessed. Furthermore, in vivo tumorigenicity assay in nude mice was performed. LPAR3 was overexpressed, whereas miR-15b was poorly expressed in ovarian cancer tissues. LPAR3 is a direct target of miR-15b. Restored miR-15b promoted Bax expression, apoptosis, and senescence, inhibited expression of LPAR3 and Bcl-2, the extent of PI3K and Akt phosphorylation, as well as ovarian cancer cell proliferation, migration, and invasion. Further, tumor growth was observed to be prevented by miR-15b overexpression. Collectively, our study demonstrates that miR-15b represses the proliferation and drives the senescence and apoptosis of ovarian cancer cells through the suppression of LPAR3 and the PI3K/Akt pathway, highlighting an antitumorigenic role of miR-15b. 相似文献
875.
876.
877.
Kai Chen Yu Yuan Ziyi Wang Dezhi Song Jinmin Zhao Zhen Cao Junhao Chen Qiang Guo Li Chen Jennifer Tickner Jiake Xu 《Journal of cellular physiology》2019,234(5):6477-6488
Excessive osteoclast formation and function are considered as the main causes of bone lytic disorders such as osteoporosis and osteolysis. Therefore, the osteoclast is a potential therapeutic target for the treatment of osteoporosis or other osteoclast-related diseases. Helvolic acid (HA), a mycotoxin originally isolated from Aspergillus fumigatus , has been discovered as an effective broad-spectrum antibacterial agent and has a wide range of pharmacological properties. Herein, for the first time, HA was demonstrated to be capable of significantly inhibiting receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in vitro by suppressing nuclear factor of activated T cells 1 (NFATc1) activation. This inhibition was followed by the dramatically decreased expression of NFATc1-targeted genes including Ctr (encoding calcitonin receptor), Acp5 (encoding tartrate-resistant acid phosphatase [TRAcP]), Ctsk (encoding cathepsin K), Atp6v0d2 (encoding the vacuolar H+ ATPase V0 subunit d2 [V-ATPase-d2]) and Mmp9 (encoding matrix metallopeptidase 9) which are osteoclastic-specific genes required for osteoclast formation and function. Mechanistically, HA was shown to greatly attenuate multiple upstream pathways including extracellular signal-regulated kinase (ERK) phosphorylation, c-Fos signaling, and intracellular Ca 2+ oscillation, but had little effect on nuclear factor-κB (NF-κB) activation. In addition, HA also diminished the RANKL-induced generation of intracellular reactive oxygen species. Taken together, our study indicated HA effectively suppressed RANKL-induced osteoclast formation and function. Thus, we propose that HA can be potentially used in the development of a novel drug for osteoclast-related bone diseases. 相似文献
878.
879.
880.