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941.
Jue‐Long Wang Chiang‐Ting Chou Kang Liu Wei‐Zhe Liang Jin‐Shiung Cheng Hong‐Tai Chang I‐Shu Chen Ti Lu Chun‐Chi Kuo Chia‐Cheng Yu Pochuen Shieh Daih‐Huang Kuo Fu‐An Chen Chung‐Ren Jan 《Journal of biochemical and molecular toxicology》2016,30(11):539-547
The effect of protriptyline on Ca2+ physiology in human hepatoma is unclear. This study explored the effect of protriptyline on [Ca2+]i and cytotoxicity in HepG2 human hepatoma cells. Protriptyline (50–150 μM) evoked [Ca2+]i rises. The Ca2+ entry was inhibited by removal of Ca2+. Protriptyline‐induced Ca2+ entry was confirmed by Mn2+‐induced quench of fura‐2 fluorescence. Except nifedipine, econazole, SKF96365, GF109203X, and phorbol 12‐myristate 13 acetate did not inhibit Ca2+ entry. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited 40% of protriptyline‐induced response. Treatment with protriptyline abolished BHQ‐induced response. Inhibition of phospholipase C (PLC) suppressed protriptyline‐evoked response by 70%. At 20–40 μM, protriptyline killed cells which was not reversed by the Ca2+ chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester (BAPTA/AM). Together, in HepG2 cells, protriptyline induced [Ca2+]i rises that involved Ca2+ entry through nifedipine‐sensitive Ca2+ channels and PLC‐dependent Ca2+ release from endoplasmic reticulum. Protriptyline induced Ca2+‐independent cell death. 相似文献
942.
943.
Oxidative stress plays a critical role in the pathogenesis of diabetic vascular complications. Trans-δ-viniferin (TVN), a polyphenolic compound, has recently attracted much attention as an antioxidant exhibiting a hypoglycemic potential. In the present study, we aimed at investigating the protective effect of TVN against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) and the potential mechanism involved. We found that TVN attenuated reactive oxygen species (ROS) production, increased catalase (CAT) activity and decreased malondialdehyde (MDA) levels to ameliorate cell survival induced by 35 mM glucose. Meanwhile, it inhibited high glucose-induced apoptosis by maintaining Ca2+ and preserving mitochondrial membrane potential (MMP) levels. The immunoblot analysis indicated that TVN efficiently regulated the cleavage of caspase family, p53, Bax and Bcl-2, all mediated by SIRT1. Furthermore, the increased level of SIRT1 induced by TVN was inhibited by nicotinamide and siRNA-medicated SIRT1 silencing (si-SIRT1), thereby confirming the significant role of SIRT1 in these events. In conclusion, our results indicated that TVN efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in high glucose-treated HUVECs. It suggested that TVN is pharmacologically promising for treating diabetic cardiovascular complications. 相似文献
944.
945.
P53 and the defenses against genome instability caused by transposons and repetitive elements 下载免费PDF全文
Arnold J. Levine David T. Ting Benjamin D. Greenbaum 《BioEssays : news and reviews in molecular, cellular and developmental biology》2016,38(6):508-513
The recent publication by Wylie et al. is reviewed, demonstrating that the p53 protein regulates the movement of transposons. While this work presents genetic evidence for a piRNA‐mediated p53 interaction with transposons in Drosophila and zebrafish, it is herein placed in the context of a decade or so of additional work that demonstrated a role for p53 in regulating transposons and other repetitive elements. The line of thought in those studies began with the observation that transposons damage DNA and p53 regulates DNA damage. The presence of transposon movement can increase the rate of evolution in the germ line and alter genes involved in signal transduction pathways. Transposition can also play an important role in cancers where the p53 gene function is often mutated. This is particularly interesting as recent work has shown that de‐repression of repetitive elements in cancer has important consequences for the immune system and tumor microenvironment. 相似文献
946.
DNA methylation differences capture substantial information about the molecular and gene-regulatory states among biological subtypes. Enrichment-based next generation sequencing methods such as MBD-isolated genome sequencing (MiGS) and MeDIP-seq are appealing for studying DNA methylation genome-wide in order to distinguish between biological subtypes. However, current analytic tools do not provide optimal features for analyzing three-group or larger study designs. MethylAction addresses this need by detecting all possible patterns of statistically significant hyper- and hypo- methylation in comparisons involving any number of groups. Crucially, significance is established at the level of differentially methylated regions (DMRs), and bootstrapping determines false discovery rates (FDRs) associated with each pattern. We demonstrate this functionality in a four-group comparison among benign prostate and three clinical subtypes of prostate cancer and show that the bootstrap FDRs are highly useful in selecting the most robust patterns of DMRs. Compared to existing tools that are limited to two-group comparisons, MethylAction detects more DMRs with strong differential methylation measurements confirmed by whole genome bisulfite sequencing and offers a better balance between precision and recall in cross-cohort comparisons. MethylAction is available as an R package at http://jeffbhasin.github.io/methylaction. 相似文献
947.
948.
Eric W. Bridgeford Shangsi Wang Zeyi Wang Ting Xu Cameron Craddock Jayanta Dey Gregory Kiar William Gray-Roncal Carlo Colantuoni Christopher Douville Stephanie Noble Carey E. Priebe Brian Caffo Michael Milham Xi-Nian Zuo Consortium for Reliability Reproducibility Joshua T. Vogelstein 《PLoS computational biology》2021,17(9)
Replicability, the ability to replicate scientific findings, is a prerequisite for scientific discovery and clinical utility. Troublingly, we are in the midst of a replicability crisis. A key to replicability is that multiple measurements of the same item (e.g., experimental sample or clinical participant) under fixed experimental constraints are relatively similar to one another. Thus, statistics that quantify the relative contributions of accidental deviations—such as measurement error—as compared to systematic deviations—such as individual differences—are critical. We demonstrate that existing replicability statistics, such as intra-class correlation coefficient and fingerprinting, fail to adequately differentiate between accidental and systematic deviations in very simple settings. We therefore propose a novel statistic, discriminability, which quantifies the degree to which an individual’s samples are relatively similar to one another, without restricting the data to be univariate, Gaussian, or even Euclidean. Using this statistic, we introduce the possibility of optimizing experimental design via increasing discriminability and prove that optimizing discriminability improves performance bounds in subsequent inference tasks. In extensive simulated and real datasets (focusing on brain imaging and demonstrating on genomics), only optimizing data discriminability improves performance on all subsequent inference tasks for each dataset. We therefore suggest that designing experiments and analyses to optimize discriminability may be a crucial step in solving the replicability crisis, and more generally, mitigating accidental measurement error. 相似文献
949.
NaCl胁迫对甘薯叶片叶绿体超微结构及一些酶活性的影响 总被引:4,自引:0,他引:4
随NaCl 胁迫浓度的提高,甘薯叶片叶绿体数目逐渐减少, 类囊体膜片层松散、扭曲、破裂并逐渐解体, 叶绿素含量下降。与此同时,H2O2 、MDA 含量增加, ASP、SOD 活性表现出先上升后下降的趋势。耐盐品种在NaCl 胁迫下能维持较强的H2O2 清除能力和较低的MDA 水平 相似文献
950.
逆转录病毒载体介导胸苷磷酸化酶在胰腺癌细胞表达 总被引:4,自引:1,他引:3
人胸腺嘧啶核苷磷酸化酶(TP)在一些肿瘤组织中活性增高,但其功能目前了解尚少。构建了表达TP的重组逆转录病毒载体,直接导入人胰腺癌PC-2细胞,mPCR扩增、Southern及Northern印迹和原位杂交证实转染细胞有外源TP的整合及表达,酶活性检测发现含外源TP细胞TP活性比PC-2细胞的内源性TP活性高TP活性高40-70倍,生长曲线和^3H-TdR参入率检测未发现含外源TP细胞生物学行为的 相似文献