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81.
Wonjong Yu Min-kyu Yang Dong Jun Sung Tae Jun Park Myungchul Kim Eustache Ntigura Sung Hea Kim Bokyung Kim Sang Woong Park Young Min Bae 《Biochemistry and Biophysics Reports》2022
As the geriatric population and life expectancy increase, the interest in preventing geriatric diseases, such as sarcopenia, is increasing. However, the causes of sarcopenia are unclear, and current diagnostic methods for sarcopenia are unreliable. We hypothesized that the changes in the expression of certain miRNAs may be associated with the pathophysiology of sarcopenia. Herein, we analyzed the miRNA expression profiles in the blood of young (3-months-old) healthy rats, old sarcopenic (17-months-old) rats, and age-matched (17-months-old) control rats. The changes in miRNA expression levels were analyzed using Bowtie 2 software. A total of 523 miRNAs were detected in the rat serum. Using scatter plots and clustering heatmap data, we found 130 miRNAs that were differentially expressed in sarcopenic rats (>2-fold change) compared to the expression in young healthy and age-matched control rats. With a threshold of >5-fold change, we identified 14 upregulated miRNAs, including rno-miR-133b-3p, rno-miR-133a-3p, rno-miR-133c, rno-miR-208a-3p, and rno-miR434-5p among others in the serum of sarcopenic rats. A protein network map based on these 14 miRNAs identified the genes involved in skeletal muscle differentiation, among which Notch1, Egr2, and Myocd represented major nodes. The data obtained in this study are potentially useful for the early diagnosis of sarcopenia and for the identification of novel therapeutic targets for the treatment and/or prevention of sarcopenia. 相似文献
82.
Kim SY Kim JY Kim SH Bae HJ Yi H Yoon SH Koo BS Kwon M Cho JY Lee CE Hong S 《FEBS letters》2007,581(5):865-871
The effect of surfactin on the proliferation of LoVo cells, a human colon carcinoma cell line, was examined. Surfactin strongly blocked the proliferation of LoVo cells by inducing pro-apoptotic activity and arresting the cell cycle, according to several lines of evidence on DNA fragmentation, Annexin V staining, and altered levels of poly (ADP-ribose) polymerase, caspase-3, p21(WAF1/Cip1), p53, CDK2 and cyclin E. The anti-proliferative activity of surfactin was mediated by inhibiting extracellular-related protein kinase and phosphoinositide 3-kinase/Akt activation, as assessed by phosphorylation levels. Therefore, our data suggest that surfactin may have anti-cancer properties as a result of its ability to downregulate the cell cycle and suppress its survival. 相似文献
83.
84.
Tariq S K Tanoli Jason C Woods Mark S Conradi Kyongtae Ty Bae David S Gierada James C Hogg Joel D Cooper Dmitriy A Yablonskiy 《Journal of applied physiology》2007,102(1):477-484
Despite a long history of development, diagnostic tools for in vivo regional assessment of lungs in patients with pulmonary emphysema are not yet readily available. Recently, a new imaging technique, in vivo lung morphometry, was introduced by our group. This technique is based on MRI measurements of diffusion of hyperpolarized (3)He gas in lung air spaces and provides quantitative in vivo tomographic information on lung microstructure at the level of the acinar airways. Compared with standard diffusivity measurements that strongly depend on pulse sequence parameters (mainly diffusion time), our approach evaluates a "hard number," the average acinar airway radius. For healthy dogs, we find here a mean acinar airway radius of approximately 0.3 mm compared with 0.36 mm in healthy humans. The purpose of the present study is the application of this technique for quantification of emphysema progression in dogs with experimentally induced disease. The diffusivity measurements and resulting acinar airway geometrical characteristics were correlated with the local lung density and local lung-specific air volume calculated from quantitative computed tomography data obtained on the same dogs. The results establish an important association between the two modalities. The observed sensitivity of our method to emphysema progression suggests that this technique has potential for the diagnosis of emphysema and tracking of disease progression or improvement via a pharmaceutical intervention. 相似文献
85.
86.
Calorie restriction (CR) and the activation of autophagy extend healthspan by delaying the onset of age-associated diseases in most living organisms. Because protein kinase CK2 (CK2) downregulation induces cellular senescence and nematode aging, we investigated CK2’s role in CR and autophagy. This study indicated that CR upregulated CK2’s expression, thereby causing SIRT1 and AMP-activated protein kinase (AMPK) activation. CK2α overexpression, including antisense inhibitors of miR-186, miR-216b, miR-337-3p, and miR-760, stimulated autophagy initiation and nucleation markers (increase in ATG5, ATG7, LC3BII, beclin-1, and Ulk1, and decrease in SQSTM1/p62). The SIRT1 deacetylase, AKT, mammalian target of rapamycin (mTOR), AMPK, and forkhead homeobox type O (FoxO) 3a were involved in CK2-mediated autophagy. The treatment with the AKT inhibitor triciribine, the AMPK activator AICAR, or the SIRT1 activator resveratrol rescued a reduction in the expression of lgg-1 (the Caenorhabditis elegans ortholog of LC3B), bec-1 (the C. elegans ortholog of beclin-1), and unc-51 (the C. elegans ortholog of Ulk1), mediated by kin-10 (the C. elegans ortholog of CK2β) knockdown in nematodes. Thus, this study indicated that CK2 acted as a positive regulator in CR and autophagy, thereby suggesting that these four miRs’ antisense inhibitors can be used as CR mimetics or autophagy inducers. 相似文献
87.
88.
Sung-Hyun Hong Gyujin Lee Changkon Park Jasung Koo Eun-Hee Kim Euiyoung Bae Jeong-Yong Suh 《Nucleic acids research》2022,50(4):2363
Bacteria and archaea use the CRISPR-Cas system to fend off invasions of bacteriophages and foreign plasmids. In response, bacteriophages encode anti-CRISPR (Acr) proteins that potently inhibit host Cas proteins to suppress CRISPR-mediated immunity. AcrIE4-F7, which was isolated from Pseudomonas citronellolis, is a fused form of AcrIE4 and AcrIF7 that inhibits both type I-E and type I-F CRISPR-Cas systems. Here, we determined the structure of AcrIE4-F7 and identified its Cas target proteins. The N-terminal AcrIE4 domain adopts a novel α-helical fold that targets the PAM interaction site of the type I-E Cas8e subunit. The C-terminal AcrIF7 domain exhibits an αβ fold like native AcrIF7, which disables target DNA recognition by the PAM interaction site in the type I-F Cas8f subunit. The two Acr domains are connected by a flexible linker that allows prompt docking onto their cognate Cas8 targets. Conserved negative charges in each Acr domain are required for interaction with their Cas8 targets. Our results illustrate a common mechanism by which AcrIE4-F7 inhibits divergent CRISPR-Cas types. 相似文献
89.
Lysine methylation is one of the most important histone modifications that modulate chromatin structure. In the present study, the roles of the histone lysine demethylases JMJD2a and LSD1 in CK2 downregulation-mediated senescence were investigated. The ectopic expression of JMJD2a and LSD1 suppressed the induction of senescence-associated β-galactosidase activity and heterochromatin foci formation as well as the reduction of colony-forming and cell migration ability mediated by CK2 knockdown. CK2 downregulation inhibited JMJD2a and LSD1 expression by activating the mammalian target of rapamycin (mTOR)-ribosomal p70 S6 kinase (p70S6K) pathway. In addition, the down-regulation of JMJD2a and LSD1 was involved in activating the p53-p21Cip1/WAF1-SUV39h1-trimethylation of the histone H3 Lys9 (H3K9me3) pathway in CK2-downregulated cells. Further, CK2 downregulation-mediated JMJD2a and LSD1 reduction was found to stimulate the dimethylation of Lys370 on p53 (p53K370me2) and nuclear import of SUV39h1. Therefore, this study indicated that CK2 downregulation reduces JMJD2a and LSD1 expression by activating mTOR, resulting in H3K9me3 induction by increasing the p53K370me2-dependent nuclear import of SUV39h1. These results suggest that CK2 is a potential therapeutic target for age-related diseases. 相似文献
90.
Kan Xiong Douglas Shea Justin Rhoades Timothy Blewett Ruolin Liu Jin
H Bae Erica Nguyen G Mike Makrigiorgos Todd R Golub Viktor
A Adalsteinsson 《Nucleic acids research》2022,50(1):e1
Accurate DNA sequencing is crucial in biomedicine. Underlying the most accurate methods is the assumption that a mutation is true if altered bases are present on both strands of the DNA duplex. We now show that this assumption can be wrong. We establish that current methods to prepare DNA for sequencing, via ‘End Repair/dA-Tailing,’ may substantially resynthesize strands, leading amplifiable lesions or alterations on one strand to become indiscernible from true mutations on both strands. Indeed, we discovered that 7–17% and 32–57% of interior ‘duplex base pairs’ from cell-free DNA and formalin-fixed tumor biopsies, respectively, could be resynthesized in vitro and potentially introduce false mutations. To address this, we present Duplex-Repair, and show that it limits interior duplex base pair resynthesis by 8- to 464-fold, rescues the impact of induced DNA damage, and affords up to 8.9-fold more accurate duplex sequencing. Our study uncovers a major Achilles’ heel in sequencing and offers a solution to restore high accuracy. 相似文献