全文获取类型
收费全文 | 23428篇 |
免费 | 1699篇 |
国内免费 | 366篇 |
出版年
2024年 | 39篇 |
2023年 | 138篇 |
2022年 | 413篇 |
2021年 | 629篇 |
2020年 | 421篇 |
2019年 | 531篇 |
2018年 | 651篇 |
2017年 | 582篇 |
2016年 | 803篇 |
2015年 | 1307篇 |
2014年 | 1447篇 |
2013年 | 1638篇 |
2012年 | 2107篇 |
2011年 | 1952篇 |
2010年 | 1223篇 |
2009年 | 1064篇 |
2008年 | 1419篇 |
2007年 | 1338篇 |
2006年 | 1134篇 |
2005年 | 1031篇 |
2004年 | 1001篇 |
2003年 | 811篇 |
2002年 | 685篇 |
2001年 | 514篇 |
2000年 | 464篇 |
1999年 | 392篇 |
1998年 | 173篇 |
1997年 | 133篇 |
1996年 | 98篇 |
1995年 | 107篇 |
1994年 | 86篇 |
1993年 | 72篇 |
1992年 | 120篇 |
1991年 | 127篇 |
1990年 | 93篇 |
1989年 | 98篇 |
1988年 | 75篇 |
1987年 | 50篇 |
1986年 | 55篇 |
1985年 | 63篇 |
1984年 | 38篇 |
1983年 | 35篇 |
1982年 | 21篇 |
1980年 | 26篇 |
1979年 | 30篇 |
1978年 | 25篇 |
1977年 | 28篇 |
1974年 | 28篇 |
1973年 | 22篇 |
1972年 | 21篇 |
排序方式: 共有10000条查询结果,搜索用时 18 毫秒
851.
Ying Zhang Wan-Li Jiang Jun-Yuan Yang Jie Huang Ganjun Kang Hai-Bo Hu Songpig Xie 《Journal of cellular physiology》2019,234(10):18679-18687
Aberrant microRNAs are widely identified in multiple cancers, including lung cancer. miR-135a-5p can function as a significant tumor regulator in diverse cancers via impacting multiple genes in oncogenic pathways. Nevertheless, the biological role of miR-135a-5p in lung cancer is poorly known. Here, we investigated its function in lung cancer. As exhibited, miR-135a-5p was elevated in lung cancer cells in contrast to BEAS-2B cells. Then, we inhibited miR-135a-5p expression by transfecting LV-anti-miR-135a-5p into lung cancer cells. As displayed, miR-135a-5p was obviously reduced in A549 and H1299 cells. Knockdown of miR-135a-5p repressed lung cancer cell growth and cell proliferation. Meanwhile, cell colony formation capacity was depressed, cell apoptosis was enhanced and cell cycle progression was blocked in G1 phase by inhibition of miR-135a-5p in vitro. Additionally, the migration and invasion of A549 and H1299 cells was strongly depressed by LV-anti-miR-135a-5p. For another, by using informatics analysis, lysyl oxidase-like 4 (LOXL4) was speculated as the downstream target of miR-135a-5p. We validated their direct correlation and moreover, overexpression of miR-135a-5p restrained LOXL4 levels in lung cancer cells. Subsequently, we proved that miR-135a-5p promoted lung cancer development via targeting LOXL4 by carrying out the in vivo assays. Taken these together, our study revealed miR-135a-5p might be indicated as a perspective for lung cancer via targeting LOXL4. 相似文献
852.
Sun-Hong Hwang Sunhoe Bang Kyung Shin Kang Deborah Kang Jongkyeong Chung 《Biochemical and biophysical research communications》2019,508(1):308-313
Wnt signaling pathway plays critical roles in body axes patterning, cell fate specification, cell proliferation, cell migration, stem cell maintenance, cancer development and etc. Deregulation of this pathway can be causative of cancer, metabolic disease and neurodegenerative disease such as Parkinson`s disease. Among the core components of Wnt signaling pathway, we discovered that Dishevelled (Dsh) interacts with ULK1 and is phosphorylated by ULK1. Unexpectedly, the knockdown of ULK1 elicited a marked increase in Wnt/β-catenin signaling. Multiple ULK1 phosphorylation sites existed on Dsh and many of them were located on the PDZ-DEP region. By using evolutionarily well conserved Drosophila Dsh, we found that S239, S247 and S254 in the PDZ-DEP region are involved in phosphorylation of Dsh by ULK1. Among these, S247 and S254 were conserved in human Dsh. When phospho-mimetic mutants (2D and 2E Dsh mutants) of these conserved residues were generated and expressed in the eyes of the fruit flies, the activity of Dsh was significantly decreased compared to wild type Dsh. Through additional alanine scanning, we further identified that S239, S247, S254, S266, S376, S554 and S555 on full length Dsh were phosphorylated by ULK1. In regards to the S266A mutation located in the PDZ domain among these phosphorylated residues, our results suggested that Dsh forms an SDS-resistant high molecular weight complex with β-catenin and TCF in the nucleus in an S266 phosphorylation-dependent manner. Based on these results, we propose that ULK1 plays a pivotal role in the regulation of Wnt/β-catenin signaling pathway by phosphorylating Dsh. 相似文献
853.
Soo Hyun Im Tatyana A. Klochkova Da Jeoung Lee Claire M. M. Gachon Gwang Hoon Kim 《Journal of phycology》2019,55(4):801-815
Disease outbreaks devastate Pyropia aquaculture farms every year. The three most common and serious diseases are Olpidiopsis‐blight and red‐rot disease caused by oomycete pathogens and green‐spot disease caused by the PyroV1 virus. We hypothesized that a basic genetic profile of molecular defenses will be revealed by comparing and analyzing the genetic response of Pyropia tenera against the above three pathogens. RNAs isolated from infected thalli were hybridized onto an oligochip containing 15,115 primers designed from P. tenera expressed sequence tags (EST)s. Microarray profiles of the three diseases were compared and interpreted together with histochemical observation. Massive amounts of reactive oxygen species accumulated in P. tenera cells exposed to oomycete pathogens. Heat shock genes and serine proteases were the most highly up‐regulated genes in all infection experiments. Genes involved in RNA metabolism, ribosomal proteins and antioxidant metabolism were also highly up‐regulated. Genetic profiles of P. tenera in response to pathogens were most similar between the two biotrophic pathogens, Olpidiopsis pyropiae and PyroV1 virus. A group of plant resistance genes were specifically regulated against each pathogen. Our results suggested that disease response in P. tenera consists of a general constitutive defense and a genetic toolkit against specific pathogens. 相似文献
854.
Flip‐flop organization in the chloroplast genome of Capsosiphon fulvescens (Ulvophyceae,Chlorophyta)
Dongseok Kim JunMo Lee Ji Won Choi Ji Hyun Yang Il‐Ki Hwang Hwan Su Yoon 《Journal of phycology》2019,55(1):214-223
To better understand organelle genome evolution of the ulvophycean green alga Capsosiphon fulvescens, we sequenced and characterized its complete chloroplast genome. The circular chloroplast genome was 111,561 bp in length with 31.3% GC content that contained 108 genes including 77 protein‐coding genes, two copies of rRNA operons, and 27 tRNAs. In this analysis, we found the two types of isoform, called heteroplasmy, were likely caused by a flip‐flop organization. The flip‐flop mechanism may have caused structural variation and gene conversion in the chloroplast genome of C. fulvescens. In a phylogenetic analysis based on all available ulvophycean chloroplast genome data, including a new C. fulvescens genome, we found three major conflicting signals for C. fulvescens and its sister taxon Pseudoneochloris marina within 70 individual genes: (i) monophyly with Ulotrichales, (ii) monophyly with Ulvales, and (iii) monophyly with the clade of Ulotrichales and Ulvales. Although the 70‐gene concatenated phylogeny supported monophyly with Ulvales for both species, these complex phylogenetic signals of individual genes need further investigations using a data‐rich approach (i.e., organelle genome data) from broader taxon sampling. 相似文献
855.
Zhenhua Chen Guanyu Chen Kang Zhou Peng Zhang Xiuli Ren Xifan Mei 《Biochemical and biophysical research communications》2019,508(2):507-511
In this paper, the effect of commonly used food sweetener (sodium cyclamate) on the proliferation and differentiation of osteoblasts has been researched. The morophology change of osteoblasts was investigated by confocal laser scanning microscopy. Cell viability was studied by MTT analysis. BMP2 expression was analyzed by western blot and immunofluorescence. Mineralization ability of osteoblasts was researched by using alizarin red staining method. The results indicate that a very low concentration (0.06?μM) of sodium cyclamate can curle and fold microfilament and microtubule of osteoblasts. The increase addition of sodium cyclamate resulted significantly decrease of cells viability. The expression of bone morphogenetic protein-2 (BMP2) was seriously suppressed by sodium cyclamate. Alizarin Red staining experiment revealed that sodium cyclamate decreased the mineralization ability of osteoblasts. The present results suggest that sodium cyclamate can seriously inhibit the proliferation and differentiation of osteoblasts. 相似文献
856.
Soonje Lee Changwoo Lee Changsu Woo Shin Jung Kang Ki Soon Shin 《Biochemical and biophysical research communications》2019,508(4):1182-1187
The ventral subiculum (vSub), a representative output structure of the hippocampus, serves as a main limbic region in mediating the brain's response to stress. There are three subtypes of subicular pyramidal neurons based on their firing patterns: regular-spiking (RS), weak-bursting (WB) and strong-bursting (SB) neurons, located differently along proximal–distal axis. Here, we found that chronic social defeat stress (CSDS) in mice increased the population of SB neurons but decreased RS neurons in the proximal vSub. Specific blockers of T-type calcium channels inhibited the burst firings with a concomitant reduction of afterdepolarization, suggesting that T-type calcium channels underlie the burst-spiking activity. Consistently, CSDS increased both T-type calcium currents and expression of Cav3.1 proteins, a subtype of T-type calcium channels, in the proximal vSub. Therefore, we conclude that CSDS-induced enhancement of Cav3.1 expression increased bursting neuronal population in the vSub, which may contribute to stress-related behaviors. 相似文献
857.
Kyung Eun Kim Eun Ae Jeong Hyun Joo Shin Jong Youl Lee Eun Bee Choi Hyeong Seok An Kyung-Ah Park Zhen Jin Dong Kun Lee Tamas L. Horvath Gu Seob Roh 《Biochemical and biophysical research communications》2019,508(1):123-129
Hypothalamic inflammation has been known as a contributor to high-fat diet (HFD)-induced insulin resistance and obesity. Myeloid-specific sirtuin 1 (SIRT1) deletion aggravates insulin resistance and hypothalamic inflammation in HFD-fed mice. Neurogranin, a calmodulin-binding protein, is expressed in the hypothalamus. However, the effects of myeloid SIRT1 deletion on hypothalamic neurogranin has not been fully clarified. To investigate the effect of myeloid SIRT1 deletion on food intake and hypothalamic neurogranin expression, mice were fed a HFD for 20 weeks. Myeloid SIRT1 knockout (KO) mice exhibited higher food intake, weight gain, and lower expression of anorexigenic proopiomelanocortin in the arcuate nucleus than WT mice. In particular, KO mice had lower ventromedial hypothalamus (VMH)-specific neurogranin expression. However, SIRT1 deletion reduced HFD-induced hypothalamic neurogranin. Furthermore, hypothalamic phosphorylated AMPK and parvalbumin protein levels were also lower in HFD-fed KO mice than in HFD-fed WT mice. Thus, these findings suggest that myeloid SIRT1 deletion affects food intake through VMH-specific neurogranin-mediated AMPK signaling and hypothalamic inflammation in mice fed a HFD. 相似文献
858.
We assessed the expression stability of several messenger (m)RNAs and micro (mi)RNAs from liver and head kidney of rainbow trout Oncorhynchus mykiss using high-throughput RNA sequencing (RNA-seq) and miRNA-seq data. Additionally, four commonly used reference genes and one small non-coding RNA (u6) were also selected to identify ideal reference mRNAs and miRNAs for quantitative real-time (qrt)-PCR analysis of heat stress responses. GeNorm, NormFinder, BestKeeper and comparative ΔCt were employed for analysis of qrt-PCR data to systematically assess the expression stability of candidate mRNAs and miRNAs and stability was ranked using geometric means. β-actin and ef1-α were the most stably expressed reference mRNAs in liver and head kidney, respectively and ssa-mir-26a-5p and ssa-mir-462b-5p were the most stably expressed miRNAs in these tissues. This is the first identification of appropriate reference mRNAs and miRNAs for qrt-PCR analysis of O. mykiss under heat stress. 相似文献
859.
860.