全文获取类型
收费全文 | 20033篇 |
免费 | 1636篇 |
国内免费 | 1726篇 |
出版年
2024年 | 17篇 |
2023年 | 258篇 |
2022年 | 292篇 |
2021年 | 1048篇 |
2020年 | 766篇 |
2019年 | 902篇 |
2018年 | 872篇 |
2017年 | 656篇 |
2016年 | 860篇 |
2015年 | 1293篇 |
2014年 | 1540篇 |
2013年 | 1596篇 |
2012年 | 1850篇 |
2011年 | 1701篇 |
2010年 | 984篇 |
2009年 | 936篇 |
2008年 | 1066篇 |
2007年 | 911篇 |
2006年 | 773篇 |
2005年 | 627篇 |
2004年 | 569篇 |
2003年 | 495篇 |
2002年 | 436篇 |
2001年 | 358篇 |
2000年 | 317篇 |
1999年 | 293篇 |
1998年 | 211篇 |
1997年 | 192篇 |
1996年 | 177篇 |
1995年 | 144篇 |
1994年 | 165篇 |
1993年 | 125篇 |
1992年 | 137篇 |
1991年 | 133篇 |
1990年 | 117篇 |
1989年 | 85篇 |
1988年 | 71篇 |
1987年 | 56篇 |
1986年 | 52篇 |
1985年 | 58篇 |
1984年 | 30篇 |
1983年 | 41篇 |
1982年 | 24篇 |
1981年 | 12篇 |
1980年 | 20篇 |
1979年 | 20篇 |
1978年 | 12篇 |
1977年 | 13篇 |
1975年 | 14篇 |
1974年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Xiao‐Xi Pan Cheng‐Chao Ruan Xiu‐Ying Liu Ling‐Ran Kong Yu Ma Qi‐Hong Wu Hai‐Qing Li Yan‐Jun Sun An‐Qing Chen Qiang Zhao Fang Wu Xiu‐Jie Wang Ji‐Guang Wang Ding‐Liang Zhu Ping‐Jin Gao 《Aging cell》2019,18(4)
Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation. 相似文献
992.
993.
Zhuoyuan Zhang Xiao Liang Yaping Fan Zhenjie Gao Laurence A. Bindoff 《Cell cycle (Georgetown, Tex.)》2019,18(9):949-962
Metformin is an antidiabetic drug widely used for the treatment of type 2 diabetes. Growing evidence suggests that it may exert antitumor effects in vivo and in vitro. However, even with the promising potency on defeating cancer cells, the pre-clinical and epidemiological studies of metformin on various kinds of cancers are not satisfactory, and the reasons and underlying mechanisms remain unknown. Since cancer is a complex system, dependent on a promoting microenvironment, we hypothesize that the interactions between cancer cells and their neighborhood fibroblasts are essential for metformin resistance. To test this, we used a cell co-culture model closely mimicking the in vivo interactions and metabolic exchanges between normal stromal cells (NOFs) and oral squamous cancer cells (OSCC). Here we show that while metformin can significantly inhibit cell growth and induce apoptosis of OSCC cultured alone in a dose-dependent manner through activating p-AMPKT172 and modulating Bcl-2, Bax, and cleaved PARP. However, when OSCC are co-cultured with NOFs the metformin effects on OSCC cells are annihilated. NOFs are rescuing OSCC from metformin – induced apoptosis, at least partially, through inhibiting the activity of AMPK and PARP, maintaining mitochondrial membrane potential and increasing the oxidative stress. Our results indicate that metformin effects on oral cancer cells are modulated by the microenvironment and that this has to be taken into consideration in the context of developing a new combination of drugs for oral cancer treatment. 相似文献
994.
Hui Shen Liming Wang Jinfeng Xiong Ci Ren Chun Gao Wencheng Ding 《Cell cycle (Georgetown, Tex.)》2019,18(10):1110-1121
Cervical cancer is a serious threat to women’s health and is the third most common malignancy in women worldwide. Recent studies indicate that the long non-coding RNA CCAT1 plays a role in the malignant behavior of many tumors. However, the role of CCAT1 in cervical cancer is still unknown. Our aim is to evaluate the expression and investigate the regulatory role and potential mechanism of CCAT1 in cervical cancer. CCAT1 expression was measured by qRT-PCR. In addition, CCK-8 assays, colony formation assays, qRT-PCR assays, Transwell assays and xenograft experiments were performed to determine the role of CCAT1 in the proliferation and invasion in cervical cancer cells. The expression of CCAT1 in the cervical cancer tissues was higher than in the adjacent normal tissues. Overexpressing CCAT1 promoted cervical cancer cell proliferation, colony formation, and invasion in vitro. Elevated CCAT1 suppressed miR-181a expression, which was accompanied by an increased expression of MMP14 and HB-EGF. In contrast, knocking down CCAT1 resulted in increased expression of miR-181a, along with decreased expression of MMP14 and HB-EGF. Thus, CCAT1 is a key oncogenic lncRNA associated with cervical cancer and plays a role in promoting cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis. 相似文献
995.
Luan Jinyu Fan Meiyong Zheng Pengfei Yang Huimin Hu Guohua Yun Binfeng Cui Yiping 《Plasmonics (Norwell, Mass.)》2019,14(1):133-138
Plasmonics - Graphene modulators based on surface plasmonic waveguides enable a strong interaction between light and graphene because great electric field enhancement occurs in the sub-wavelength... 相似文献
996.
997.
998.
Guangyi Fan Yaolei Zhang Xiaochuan Liu Jiahao Wang Zeguo Sun Shuai Sun He Zhang Jianwei Chen Meiqi Lv Kai Han Xiaoxuan Tan Jie Hu Rui Guan Yuanyuan Fu Shanshan Liu Xi Chen Qiwu Xu Yating Qin Longqi Liu Jie Bai Ou Wang Jingbo Tang Haorong Lu Zhouchun Shang Bo Wang Guohai Hu Xia Zhao Yan Zou Ao Chen Meihua Gong Wenwei Zhang Simon M.‐Y. Lee Songhai Li Junnian Liu Zhen Li Yishan Lu Jamal S. M. Sabir Mumdooh J. Sabir Muhummadh Khan Nahid H. Hajrah Ye Yin Karsten Kristiansen Huanming Yang Jian Wang Xun Xu Xin Liu 《Molecular ecology resources》2019,19(4):944-956
Marine mammals are important models for studying convergent evolution and aquatic adaption, and thus reference genomes of marine mammals can provide evolutionary insights. Here, we present the first chromosome‐level marine mammal genome assembly based on the data generated by the BGISEQ‐500 platform, for a stranded female sperm whale (Physeter macrocephalus). Using this reference genome, we performed chromosome evolution analysis of the sperm whale, including constructing ancestral chromosomes, identifying chromosome rearrangement events and comparing with cattle chromosomes, which provides a resource for exploring marine mammal adaptation and speciation. We detected a high proportion of long interspersed nuclear elements and expanded gene families, and contraction of major histocompatibility complex region genes which were specific to sperm whale. Using comparisons with sheep and cattle, we analysed positively selected genes to identify gene pathways that may be related to adaptation to the marine environment. Further, we identified possible convergent evolution in aquatic mammals by testing for positively selected genes across three orders of marine mammals. In addition, we used publicly available resequencing data to confirm a rapid decline in global population size in the Pliocene to Pleistocene transition. This study sheds light on the chromosome evolution and genetic mechanisms underpinning sperm whale adaptations, providing valuable resources for future comparative genomics. 相似文献
999.
Hongmei Zhu Wenke Li Zhuole Wang Jianguo Chen Mingxing Ding Li Han 《Microbial biotechnology》2019,12(6):1337-1345
Endometritis, which is usually caused by bacterial infection, is characterized by high levels of pro-inflammatory cytokines and a high infertility rate. Triggering receptor expressed on myeloid cells-1 (TREM-1) has been recognized as a potent amplifier of inflammatory reactions. Studies have demonstrated reduced inflammatory responses and mortality rates of animals with bacterial infection due to the blocking of TREM-1 expression. However, whether TREM-1 deficiency could alleviate the inflammatory reaction in bacterial endometritis is still unclear. Here, TREM-1 knock-out (Trem-1−/−) mice were used to inhibit TREM-1 signalling to evaluate its role in inflammatory reactions after a highly pathogenic LPS infection in mice uteri. The results demonstrated that TREM-1 deficiency attenuated the inflammation in mice uteri; markedly reduced the number of polymorphonuclear neutrophils; and suppressed interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) concentrations in serum as well as their production in inflamed uteri after LPS stimulation. Our results illustrate an anticipated pathogenic impact of TREM-1 on endometritis during LPS infection and indicate that blocking of TREM-1 in LPS-induced endometritis holds considerable promise for blunting excessive inflammation. 相似文献
1000.
Fan Meng Ruifeng Li Liyu Ma Lifang Liu Xiaorong Lai Dongyang Yang Junmin Wei Dong Ma Zijun Li 《Microbes and infection / Institut Pasteur》2019,21(7):296-304
Esophageal carcinoma, with a increasing incidence, is one of the most aggressive carcinomas in gastrointestinal tract. Epidemiologic studies demonstrate an association of oral pathogens with multiple diseases, including rheumatoid arthritis, cardiovascular diseases, diabetes, and gastrointestinal malignancies. Nevertheless, a causal relationship between oral pathogens and esophageal squamous cell carcinoma (ESCC) has not been elucidated. Here, we found that Porphyromonas was significantly enriched in the saliva of patients with ESCC, compared with that in normal human. In vitro studies showed that Porphyromonas gingivalis (P. gingivalis) promoted the proliferation and motility of ESCC cells, as evidenced by up regulated expression of key molecules implicated in NF-κB signaling pathway. These findings, for the first time, demonstrated a role of oral pathogens in inducing ESCC tumorigenesis and metastasis, which might involve regulation of NF-κB signaling pathway. 相似文献