全文获取类型
收费全文 | 5655篇 |
免费 | 489篇 |
国内免费 | 534篇 |
出版年
2024年 | 10篇 |
2023年 | 80篇 |
2022年 | 194篇 |
2021年 | 343篇 |
2020年 | 225篇 |
2019年 | 247篇 |
2018年 | 273篇 |
2017年 | 187篇 |
2016年 | 223篇 |
2015年 | 377篇 |
2014年 | 371篇 |
2013年 | 488篇 |
2012年 | 527篇 |
2011年 | 484篇 |
2010年 | 258篇 |
2009年 | 259篇 |
2008年 | 295篇 |
2007年 | 258篇 |
2006年 | 196篇 |
2005年 | 190篇 |
2004年 | 144篇 |
2003年 | 145篇 |
2002年 | 111篇 |
2001年 | 123篇 |
2000年 | 89篇 |
1999年 | 108篇 |
1998年 | 62篇 |
1997年 | 49篇 |
1996年 | 40篇 |
1995年 | 45篇 |
1994年 | 38篇 |
1993年 | 25篇 |
1992年 | 41篇 |
1991年 | 25篇 |
1990年 | 24篇 |
1989年 | 25篇 |
1988年 | 20篇 |
1987年 | 15篇 |
1986年 | 19篇 |
1985年 | 20篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 7篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有6678条查询结果,搜索用时 125 毫秒
61.
62.
Jordan Bai Muhammad Farid Abdul-Rahman Anne Rifkin-Graboi Yap-Seng Chong Kenneth Kwek Seang-Mei Saw Keith M. Godfrey Peter D. Gluckman Marielle V. Fortier Michael J. Meaney Anqi Qiu 《PloS one》2012,7(10)
We studied a sample of 75 Chinese, 73 Malay, and 29 Indian healthy neonates taking part in a cohort study to examine potential differences in neonatal brain morphology and white matter microstructure as a function of ethnicity using both structural T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). We first examined the differences in global size and morphology of the brain among the three groups. We then constructed the T2-weighted MRI and DTI atlases and employed voxel-based analysis to investigate ethnic differences in morphological shape of the brain from the T2-weighted MRI, and white matter microstructure measured by fractional anisotropy derived from DTI. Compared with Malay neonates, the brains of Indian neonates’ tended to be more elongated in anterior and posterior axis relative to the superior-inferior axis of the brain even though the total brain volume was similar among the three groups. Although most anatomical regions of the brain were similar among Chinese, Malay, and Indian neonates, there were anatomical variations in the spinal-cerebellar and cortical-striatal-thalamic neural circuits among the three populations. The population-related brain regions highlighted in our study are key anatomical substrates associated with sensorimotor functions. 相似文献
63.
Jin Cui Xiaoqun Li Sicheng Wang Yiming Su Xiao Chen Liehu Cao Xin Zhi Zili Qiu Yao Wang Hao Jiang Biaotong Huang Fang Ji Jiacan Su 《Journal of cellular and molecular medicine》2020,24(11):6149-6161
Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro-architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti-cancer, anti-inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K-AKT-NFATc1 pathway is one of the most important downstream pathways of RANKL-induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K-AKT-NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM-p53-induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy-induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti-cancer drug triptolide was demonstrated to be anti-osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour. 相似文献
64.
Xi Xiang Hui Liu Liyun Wang Bihui Zhu Lang Ma Fangxue Du Ling Li Li Qiu 《Journal of cellular and molecular medicine》2020,24(18):10816-10829
Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell‐derived factor‐1α (SDF‐1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF‐1α‐loaded microbubbles MB(SDF‐1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF‐1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF‐1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF‐1α) through covalent bonding with impressive SDF‐1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF‐1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF‐1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF‐1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA. 相似文献
65.
Chen Zhou Guowen Shen Fan Yang Jingling Duan Zhen Wu Mingqing Yang Yi Liu Xueli Du Xiaoling Zhang Shengjun Xiao 《Journal of cellular and molecular medicine》2020,24(11):6438-6447
Cisplatin resistance is one of the main obstacles in the treatment of advanced nasopharyngeal carcinoma (NPC). AKR1C1 is a member of the Aldo-keto reductase superfamily (AKRs), which converts aldehydes and ketones to their corresponding alcohols and has been reported to be involved in chemotherapeutic resistance of multiple drugs. The expression and function of AKR1C1 in NPC have not been reported until now. The aim of this research was to investigate the expression of AKR1C1 and it is role in cisplatin resistance in NPC. AKR1C1 protein expression was detected by immunohistochemistry in human NPC tissues and by Western blot assays in NPC and immortalized nasopharyngeal epithelial cells. The effects of AKR1C1 knock-down by siRNA on proliferation, migration and invasion in NPC cells were evaluated by CCK8, wound healing and transwell assays. To evaluate the effects of AKR1C1 silencing on cisplatin sensitivity in NPC cells, CCK8 assays were used to detect cell proliferation, flow cytometry was used to detect cell cycle distribution, and flow cytometry and DAPI staining were used to detect cell apoptosis. AKR1C1 down-regulation was associated with advanced clinicopathological characters such as larger tumor size, more lymphatic nodes involvement, with metastasis and later clinical stages, while AKR1C1 down-regulation was a good prognostic factor for overall survival (OS) in NPC patients. In vitro study showed that AKR1C1 was not directly involved in the malignant biological behaviours such as proliferation, cell cycle progression and migration of NPC cells, whereas AKR1C1 knock-down could enhance cisplatin sensitivity of NPC cells. These results suggest that AKR1C1 is a potential marker for predicting cisplatin response and could serve as a molecular target to increase cisplatin sensitivity in NPC. 相似文献
66.
67.
Wu‐Xia Qiu Xiao‐Li Ma Xiao Lin Fan Zhao Di‐Jie Li Zhi‐Hao Chen Ke‐Wen Zhang Ru Zhang Pai Wang Yun‐Yun Xiao Zhi‐Ping Miao Kai Dang Xiao‐Yang Wu Ai‐Rong Qian 《Journal of cellular and molecular medicine》2020,24(1):317-327
Microtubule actin cross‐linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3‐E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast‐specific Osterix (Osx) promoter‐driven Macf1 conditional knockout mice (Macf1f/fOsx‐Cre). The Macf1f/fOsx‐Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1f/fOsx‐Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1f/fOsx‐Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1f/fOsx‐Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease. 相似文献
68.
69.
Yuping Chen Ni Jiao Ming Jiang Liping Liu Yihui Zhu Hongyan Wu Jing Chen Yingxue Fu Qiu Du Huiqin Xu Jihu Sun 《Journal of cellular and molecular medicine》2020,24(11):6083-6095
Diabetes mellitus (DM) damages male reproduction at multiple levels, such as endocrine secretion, spermatogenesis and penile erection. We herein investigated the protective effects and mechanism of loganin targeting the advanced glycation end products (AGEs)/receptor for AGEs (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/NF-κB signalling pathway. Loganin relieved the general DM symptoms and decreased the blood glucose level of KK-Ay DM mice. Haematoxylin-eosin staining demonstrated that loganin ameliorated testicular histology and function and enhanced the activities of testis-specific markers lactate dehydrogenase (LDH), acid phosphatase (ACP) and gamma-glutamyl transferase (γ-GT). Loganin also showed evident anti-oxidative stress, anti-apoptotic and anti-inflammatory effects on DM-induced reproductive damage by restoring glutathione (GSH) level and superoxide dismutase (SOD) activity, as well as reducing reactive oxygen species (ROS) level and Bax/Bcl-2 ratio in vivo and in vitro. Western blotting exhibited that loganin significantly inhibited the AGEs/RAGE/p38MAPK/NF-κB signalling pathway. Acridine orange and ethidium bromide staining (AOEB) and Western blotting showed that loganin in combination with inhibitors of RAGE, p38MAPK and NF-κB exerted stronger anti-apoptotic effects on AGE-induced GC-2 cell damage compared with loganin alone. In conclusion, loganin can protect against DM-induced reproductive damage, probably by suppressing the AGEs/RAGE/p38MAPK/NF-κB pathway. 相似文献
70.
Dafei Chai Dong Qiu Zichun Zhang Shang Yuchen Shi Gang Wang Lin Fang Huizhong Li Hailong Li Hui Tian Junnian Zheng 《Journal of cellular and molecular medicine》2020,24(18):10744-10755
Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIXpromotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIXpromotor‐AIM2 adenoviruses (Ad‐CAIXpromotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIXpromotor, Ad‐CAIXpromotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIXpromotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIXpromotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIXpromotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIXpromotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours. 相似文献