全文获取类型
收费全文 | 5049篇 |
免费 | 427篇 |
国内免费 | 563篇 |
学科分类
生物科学 | 6039篇 |
出版年
2024年 | 10篇 |
2023年 | 72篇 |
2022年 | 114篇 |
2021年 | 301篇 |
2020年 | 219篇 |
2019年 | 255篇 |
2018年 | 221篇 |
2017年 | 202篇 |
2016年 | 248篇 |
2015年 | 336篇 |
2014年 | 379篇 |
2013年 | 441篇 |
2012年 | 447篇 |
2011年 | 426篇 |
2010年 | 263篇 |
2009年 | 263篇 |
2008年 | 269篇 |
2007年 | 215篇 |
2006年 | 238篇 |
2005年 | 171篇 |
2004年 | 133篇 |
2003年 | 104篇 |
2002年 | 85篇 |
2001年 | 59篇 |
2000年 | 53篇 |
1999年 | 77篇 |
1998年 | 47篇 |
1997年 | 49篇 |
1996年 | 48篇 |
1995年 | 52篇 |
1994年 | 38篇 |
1993年 | 32篇 |
1992年 | 30篇 |
1991年 | 20篇 |
1990年 | 12篇 |
1989年 | 17篇 |
1988年 | 16篇 |
1987年 | 15篇 |
1986年 | 7篇 |
1985年 | 16篇 |
1984年 | 8篇 |
1983年 | 9篇 |
1982年 | 6篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1975年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有6039条查询结果,搜索用时 15 毫秒
81.
82.
83.
84.
Yizhi Jiang Dongping Huang Yuji Kondo Miao Jiang Zhenni Ma Lu Zhou Jian Su Xia Bai Changgeng Ruan Zhaoyue Wang Lijun Xia 《Journal of cellular and molecular medicine》2020,24(7):4356-4361
Hereditary thrombotic thrombocytopenic purpura (TTP) is an autosomal recessive thrombosis disorder, caused by loss-of-function mutations in ADAMTS13. Mutations in the CUB domains of ADAMTS13 are rare, and the exact mechanisms through which these mutations result in the development of TTP have not yet been fully elucidated. In this study, we identified two novel mutations in the CUB domains in a TTP family with an acceptor splice-site mutation (c.3569−1, G>A, intron 25) and a point missense mutation (c.3923, G>A, exon 28), resulting in a glycine to aspartic acid substitution (p.G1308D). In vitro splicing analysis revealed that the intronic mutation resulted in abnormal pre-mRNA splicing, and an in vitro expression assay revealed that the missense mutation significantly impaired ADAMTS13 secretion. Although both the patient and her brother displayed significantly reduced ADAMTS13 activity and increased levels of ultra-large VWF (ULVWF) multimers in plasma, only the female developed acute episodes of TTP. Our findings indicate the importance of the CUB domains for the protein stability and extracellular secretion of ADAMTS13. 相似文献
85.
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
86.
Identification of novel susceptibility loci for non‐syndromic cleft lip with or without cleft palate
Lan Ma Shu Lou Ziyue Miao Siyue Yao Xin Yu Shiyi Kan Guirong Zhu Fan Yang Chi Zhang Weibing Zhang Meilin Wang Lin Wang Yongchu Pan 《Journal of cellular and molecular medicine》2020,24(23):13669
Although several genome‐wide association studies (GWAS) of non‐syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in‐depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case‐parent trios and another in‐house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3’ of SERTAD4, P = 6.44 × 10−14; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10−13 and 2.80 × 10−11, respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10−6; rs2095293: intron of NR6A1, P = 2.98 × 10−5). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10−16). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down‐regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population. 相似文献
87.
88.
Jie Ouyang Zhihao Shu Shuhua Chen Hong Xiang Hongwei Lu 《Journal of cellular and molecular medicine》2020,24(18):10290-10301
There are many different types of cardiovascular diseases, which impose a huge economic burden due to their extremely high mortality rates, so it is necessary to explore the underlying mechanisms to achieve better supportive and curative care outcomes. Sphingosine 1‐phosphate (S1P) is a bioactive lipid mediator with paracrine and autocrine activities that acts through its cell surface S1P receptors (S1PRs) and intracellular signals. In the circulatory system, S1P is indispensable for both normal and disease conditions; however, there are very different views on its diverse roles, and its specific relevance to cardiovascular pathogenesis remains elusive. Here, we review the synthesis, release and functions of S1P, specifically detail the roles of S1P and S1PRs in some common cardiovascular diseases, and then address several controversial points, finally, we focus on the development of S1P‐based therapeutic approaches in cardiovascular diseases, such as the selective S1PR1 modulator amiselimod (MT‐1303) and the non‐selective S1PR1 and S1PR3 agonist fingolimod, which may provide valuable insights into potential therapeutic strategies for cardiovascular diseases. 相似文献
89.
Dafeng Yang Zhousheng Yang Lei Chen Dabin Kuang Yang Zou Jie Li Xu Deng Songyuan Luo Jianfang Luo Jun He Miao Yan Guixia He Yang Deng Rong Li Qiong Yuan Yangzhao Zhou Pei Jiang Shenglan Tan 《Journal of cellular and molecular medicine》2020,24(10):5911-5925
Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe−/−) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe−/− mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe−/− mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management. 相似文献
90.