全文获取类型
收费全文 | 17424篇 |
免费 | 1541篇 |
国内免费 | 2561篇 |
出版年
2024年 | 18篇 |
2023年 | 170篇 |
2022年 | 294篇 |
2021年 | 799篇 |
2020年 | 644篇 |
2019年 | 790篇 |
2018年 | 735篇 |
2017年 | 585篇 |
2016年 | 775篇 |
2015年 | 1151篇 |
2014年 | 1322篇 |
2013年 | 1355篇 |
2012年 | 1762篇 |
2011年 | 1557篇 |
2010年 | 961篇 |
2009年 | 917篇 |
2008年 | 1085篇 |
2007年 | 968篇 |
2006年 | 897篇 |
2005年 | 776篇 |
2004年 | 654篇 |
2003年 | 647篇 |
2002年 | 524篇 |
2001年 | 362篇 |
2000年 | 296篇 |
1999年 | 300篇 |
1998年 | 181篇 |
1997年 | 173篇 |
1996年 | 151篇 |
1995年 | 113篇 |
1994年 | 111篇 |
1993年 | 68篇 |
1992年 | 78篇 |
1991年 | 53篇 |
1990年 | 45篇 |
1989年 | 41篇 |
1988年 | 27篇 |
1987年 | 25篇 |
1986年 | 21篇 |
1985年 | 33篇 |
1984年 | 16篇 |
1983年 | 13篇 |
1982年 | 9篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1971年 | 2篇 |
1966年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 24 毫秒
951.
952.
Peigang Ji Liang Wang Jinghui Liu Ping Mao Ruichun Li Haitao Jiang Miao Lou Meng Xu Xiao Yu 《Journal of cellular biochemistry》2019,120(3):3259-3267
Ribosomal protein L34 (RPL34), belonging to the L34E family of ribosomal proteins, was reported to be dysregulated in several types of cancers and plays important roles in tumor progression. However, the expression and roles of RPL34 in human glioma remain largely unknown. Thus, the objective of this study was to investigate the expression and role of RPL34 in glioma. We report here that RPL34 is highly expressed in human glioma tissues and cell lines. Knockdown of RPL34 markedly inhibited the proliferation, migration, and invasion, as well as prevented the epithelial-mesenchymal transition phenotype in glioma cells. Further, mechanistic analysis showed that knockdown of RPL34 significantly downregulated the levels of p-JAK and p-STAT3 in glioma cells. Taken together, our findings indicated that knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK/STAT3 signaling pathway. Thus, RPL34 may serve as a potential therapeutic target for the treatment of glioma. 相似文献
953.
Chunlei Miao Dengke Qin Peigang Cao Ping Lu Yutong Xia Mengjiao Li Miao Sun Wei Zhang Fanghong Yang Yingjie Zhang Shengjian Tang Tianyi Liu Fangjun Liu 《Journal of cellular biochemistry》2019,120(5):8754-8763
Bone morphogenetic protein (BMP)2/7 heterodimer shows greater efficacy in enhancing bone regeneration. However, the precise mechanism and the role of mitogen-activated protein kinase (MAPK) signaling network in BMP2/7-driven osteogenesis remain ambiguous. In this study, we evaluated the effects of BMP2/7 heterodimers on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (BMSCs), with the aim to elaborate how MAPKs might be involved in this cellular process by treatment of rat BMSCs with BMP2/-7 with a special signal-pathway inhibitor. We found that BMP2/7 heterodimer induced a much stronger osteogenic response in rat BMSCs compared with either homodimer. Most interestingly, extracellular signal-regulated kinase (ERK) demonstrated a highly sustained phosphorylation and activation in the BMP2/7 heterodimer treatment groups, and inhibition of ERK cascades using U0126 special inhibitor that significantly reduced the activity of ALP and calcium mineralization to a substantial degree in rat BMSCs treated with BMP2/7 heterodimers. Collectively, we demonstrate that BMP2/7 heterodimer shows a potent ability to stimulate osteogenesis in rat BMSCs. The activated ERK signaling pathway involved in this process may contribute partially to an increased osteogenic potency of heterodimeric BMP2/7 growth factors. 相似文献
954.
955.
956.
Xiaorui Cui Mingpeng Li Zhengchu He Lin Hu Jianping Liu Jianhui Yan Liming Hua 《Cell biochemistry and function》2020,38(8):1025-1035
957.
Human insulin from a precursor overexpressed in the methylotrophic yeast Pichia pastoris and a simple procedure for purifying the expression product 总被引:12,自引:0,他引:12
Wang Y Liang ZH Zhang YS Yao SY Xu YG Tang YH Zhu SQ Cui DF Feng YM 《Biotechnology and bioengineering》2001,73(1):74-79
The methylotrophic yeast Pichia pastoris, which proved successful in producing many heterologous proteins, was used to express an insulin precursor. A transformant with a high copy number of the gene integrated into the chromosome was obtained by the dot-blotting method. In high-density fermentation using a simple culture medium composed mainly of salt and methanol, the expression level reached 1.5 g/L. A simple two-step method was established to purify the expression product from the culture medium with an overall recovery of about 80%. After tryptic transpeptidation, human insulin with full receptor binding capacity and biological activity was obtained. In the presence of zinc, the recombinant human insulin could be crystallized in the rhombohedral form. 相似文献
958.
959.
Tiffany HL Lavigne MC Cui YH Wang JM Leto TL Gao JL Murphy PM 《The Journal of biological chemistry》2001,276(26):23645-23652
Amyloid-beta, the pathologic protein in Alzheimer's disease, induces chemotaxis and production of reactive oxygen species in phagocytic cells, but mechanisms have not been fully defined. Here we provide three lines of evidence that the phagocyte G protein-coupled receptor (N-formylpeptide receptor 2 (FPR2)) mediates these amyloid-beta-dependent functions in phagocytic cells. First, transfection of FPR2, but not related receptors, including the other known N-formylpeptide receptor FPR, reconstituted amyloid-beta-dependent chemotaxis and calcium flux in HEK 293 cells. Second, amyloid-beta induced both calcium flux and chemotaxis in mouse neutrophils (which express endogenous FPR2) with similar potency as in FPR2-transfected HEK 293 cells. This activity could be specifically desensitized in both cell types by preincubation with a specific FPR2 agonist, which desensitizes the receptor, or with pertussis toxin, which uncouples it from G(i)-dependent signaling. Third, specific and reciprocal desensitization of superoxide production was observed when N-formylpeptides and amyloid-beta were used to sequentially stimulate neutrophils from FPR -/- mice, which express FPR2 normally. Potential biological relevance of these results to the neuroinflammation associated with Alzheimer's disease was suggested by two additional findings: first, FPR2 mRNA could be detected by PCR in mouse brain; second, induction of FPR2 expression correlated with induction of calcium flux and chemotaxis by amyloid-beta in the mouse microglial cell line N9. Further, in sequential stimulation experiments with N9 cells, N-formylpeptides and amyloid-beta were able to reciprocally cross-desensitize each other. Amyloid-beta was also a specific agonist at the human counterpart of FPR2, the FPR-like 1 receptor. These results suggest a unified signaling mechanism for linking amyloid-beta to phagocyte chemotaxis and oxidant stress in the brain. 相似文献
960.
Segregation analyses of 1,476 population-based Australian families affected by prostate cancer 下载免费PDF全文
Cui J Staples MP Hopper JL English DR McCredie MR Giles GG 《American journal of human genetics》2001,68(5):1207-1218
Segregation analyses aim to detect genetic factors that have a major effect on an individual's risk of disease and to describe them in terms of mode of inheritance, age-specific cumulative risk (penetrance), and allele frequency. We conducted single- and two-locus segregation analyses of data from 1,476 men with prostate cancer diagnosed at age <70 years and ascertained through population registries in Melbourne, Sydney, and Perth, Australia, and from their brothers, fathers, and both maternal and paternal lineal uncles. Estimation and model selection were based on asymptotic likelihood theory and were performed through use of the software MENDEL. All two-locus models gave better fits than did single-locus models, even if lineal uncles were excluded or if we censored data (age and disease status) for relatives at 1992, when prostate-specific-antigen testing started to have a major impact on the incidence of prostate cancer in Australia. Among the genetic models that we considered, the best-fitting ones included a dominantly inherited increased risk that was greater, in multiplicative terms, at younger ages, as well as a recessively inherited or X-linked increased risk that was greater, in multiplicative terms, at older ages. The recessive and X-linked effects were strongly confounded, and it was not possible to fit them together. Penetrance to age 80 years was approximately 70% (95% confidence interval [CI] 57%-85%) for the dominant effect and virtually 100% for the recessive and X-linked effects. Approximately 1/30 (95% CI 1/80-1/12) men would carry the dominant risk, and 1/140 (95% CI 1/220-1/90) would carry the recessive risk or 1/200 (95% CI 1/380-1/100) would carry the X-linked risk. Within discussed limitations, these analyses confirm the genetic heterogeneity, of prostate cancer susceptibility, that is becoming evident from linkage analyses, and they may aid future efforts in gene discovery. 相似文献