全文获取类型
收费全文 | 4088篇 |
免费 | 388篇 |
国内免费 | 236篇 |
出版年
2024年 | 3篇 |
2023年 | 37篇 |
2022年 | 95篇 |
2021年 | 208篇 |
2020年 | 123篇 |
2019年 | 160篇 |
2018年 | 176篇 |
2017年 | 130篇 |
2016年 | 172篇 |
2015年 | 283篇 |
2014年 | 287篇 |
2013年 | 341篇 |
2012年 | 357篇 |
2011年 | 346篇 |
2010年 | 206篇 |
2009年 | 175篇 |
2008年 | 236篇 |
2007年 | 194篇 |
2006年 | 152篇 |
2005年 | 160篇 |
2004年 | 114篇 |
2003年 | 118篇 |
2002年 | 89篇 |
2001年 | 84篇 |
2000年 | 69篇 |
1999年 | 69篇 |
1998年 | 42篇 |
1997年 | 38篇 |
1996年 | 37篇 |
1995年 | 38篇 |
1994年 | 27篇 |
1993年 | 20篇 |
1992年 | 24篇 |
1991年 | 24篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 12篇 |
1987年 | 13篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有4712条查询结果,搜索用时 46 毫秒
981.
982.
Weiwen Zheng Ulla Rasmussen Siping Zheng Xiaodong Bao Bin Chen Yuan Gao Xiong Guan John Larsson Birgitta Bergman 《PloS one》2013,8(6)
Programmed cell death (PCD) is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20%) of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays), together with visualization of cytoskeleton alterations (FITC-phalloidin staining), showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20) further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom. 相似文献
983.
Two‐stage orthogonality based estimation for semiparametric varying‐coefficient models and its applications in analyzing AIDS data
下载免费PDF全文
![点击此处可从《Biometrical journal. Biometrische Zeitschrift》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yan‐Yong Zhao Jin‐Guan Lin Xu‐Guo Ye Hong‐Xia Wang Xing‐Fang Huang 《Biometrical journal. Biometrische Zeitschrift》2018,60(1):79-99
Semiparametric smoothing methods are usually used to model longitudinal data, and the interest is to improve efficiency for regression coefficients. This paper is concerned with the estimation in semiparametric varying‐coefficient models (SVCMs) for longitudinal data. By the orthogonal projection method, local linear technique, quasi‐score estimation, and quasi‐maximum likelihood estimation, we propose a two‐stage orthogonality‐based method to estimate parameter vector, coefficient function vector, and covariance function. The developed procedures can be implemented separately and the resulting estimators do not affect each other. Under some mild conditions, asymptotic properties of the resulting estimators are established explicitly. In particular, the asymptotic behavior of the estimator of coefficient function vector at the boundaries is examined. Further, the finite sample performance of the proposed procedures is assessed by Monte Carlo simulation experiments. Finally, the proposed methodology is illustrated with an analysis of an acquired immune deficiency syndrome (AIDS) dataset. 相似文献
984.
Yuling Zhong Yubing Liang Jing Chen Li Li Yi Qin Enjian Guan Dan He Yi Wei Yubo Xie Qiang Xiao 《Cell biochemistry and function》2014,32(8):720-729
Propofol is widely used in paediatric anaesthesia and intensive care unit because of its essentially short‐acting anaesthetic effect. Recent data have shown that propofol induced neurotoxicity in developing brain. However, the mechanisms are not extremely clear. To gain a better insight into the toxic effects of propofol on hippocampal neurons, we treated cells at the days in vitro 7 (DIV 7), which were prepared from Sprague–Dawley embryos at the 18th day of gestation, with propofol (0.1–1000 μM) for 3 h. A significant decrease in neuronal proliferation and a remarkable increase in neuroapoptosis were observed in DIV 7 hippocampal neurons as measured by 3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and apoptosis assay respectively. Moreover, propofol treatment decreased the nuclear factor kappaB (NF‐κB) p65 expression, which was accompanied by a reduction in B‐cell lymphoma 2 (Bcl‐2) mRNA and protein levels, increased caspase‐3 mRNA and activation of caspase‐3 protein. These results indicated that downregulation of NF‐κB p65 and Bcl‐2 were involved in the potential mechanisms of propofol‐induced neurotoxicity. This likely led to the caspase‐3 activation, triggered apoptosis and inhibited the neuronal growth and proliferation that we have observed in our in vitro systems. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
985.
Jian Zhang Sheng Yang Hongmei Guan Jueyu Zhou Yuan Gao 《Journal of cellular and molecular medicine》2021,25(3):1688-1699
Xanthatin (Xa) is a bicyclic sesquiterpene lactone identified from the plant Xanthium L. with impressive antitumor activity, but the role of Xa in non-small cell lung cancer (NSCLC) is not known. Here we found that Xa inhibits proliferation, migration, invasion and induces apoptosis in NSCLC cells. RNA sequencing and Gene set enrichment analysis revealed that Xa significantly activates p53 pathway and suppresses E2F targets, G2M checkpoint and MYC targets in A549 cells. Among these changed genes, the down-regulated gene BARD1 triggered by Xa was identified as a candidate involved in Xa’s antitumor effect because of its vital role in homologous recombination (HR). Further studies demonstrated that Xa inhibits HR through the BARD1/BRCA1/RAD51 axis, which enhances cell sensitivity to cisplatin. Mechanistic studies showed that Xa inhibits BARD1 through the JAK2/STAT4 pathway. Our study revealed that Xa is a promising drug to treat NSCLC, especially in combination with conventional chemotherapy. 相似文献
986.
987.
Adriano Senatore Wendy Guan Adrienne N. Boone J. David Spafford 《The Journal of biological chemistry》2014,289(17):11952-11969
T-type (Cav3) channels are categorized as calcium channels, but invertebrate ones can be highly sodium-selective channels. We illustrate that the snail LCav3 T-type channel becomes highly sodium-permeable through exon splicing of an extracellular turret and descending helix in domain II of the four-domain Cav3 channel. Highly sodium-permeable T-type channels are generated without altering the invariant ring of charged residues in the selectivity filter that governs calcium selectivity in calcium channels. The highly sodium-permeant T-type channel expresses in the brain and is the only splice isoform expressed in the snail heart. This unique splicing of turret residues offers T-type channels a capacity to serve as a pacemaking sodium current in the primitive heart and brain in lieu of Nav1-type sodium channels and to substitute for voltage-gated sodium channels lacking in many invertebrates. T-type channels would also contribute substantially to sodium leak conductances at rest in invertebrates because of their large window currents. 相似文献
988.
Ji-ye Yin He-mei Wang Quan-jun Wang Yan-sheng Dong Gang Han Yong-biao Guan Ke-yong Zhao Wen-sheng Qu Ye Yuan Xiao-xin Gao Shu-fang Jing Ri-gao Ding 《PloS one》2014,9(4)
The objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular administration of 6 mg kg-1 artemether induced a decreased red blood cell (RBC) count (anemia), concurrent extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT interval and neuropathic changes in the central nervous system, which demonstrated the cortex and motor neuron vulnerability, but no behavioral changes. Following treatment with artesunate, we observed a decreased heart rate, which was most likely due to cardiac conduction system damage, as well as a deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. However, in contrast to treatment with artemether, neurotoxicity was not observed following treatment with artesunate. In addition, ultra-structural examination by transmission electron microscopy showed mitochondrial damage following treatment with artesunate. These findings demonstrated the spectrum of toxic changes that result upon treatment with artesunate and artemether and show that the prolonged administration of low doses of these derivatives result in diverse toxicity profiles. 相似文献
989.
990.
The ability of nineteen tryptamine derivatives to interact with putative 5-hydroxytryptamine1D (5-HT1D) receptor binding sites in bovine caudate was analyzed. Sixteen of the nineteen agents competed, with variable potency, for these binding sites with Hill slopes of approximately unity. By contrast, 5-carboxyamidotryptamine (5-CT), sumatriptan and 5-benzyloxytryptamine (5-BT) competed with Hill slope values significantly less than unity. These three drugs share, in comparison to the sixteen other tryptamines, relatively large substitutions at the 5-position of the indole moiety. Additional radioligand binding studies with 5-BT indicate that the drug shows relative selectivity for 5-HT1D/1B binding sites. Functionally, 5-BT and sumatriptan inhibit 3H-5-HT release from guinea pig cortical synaptosomes with equal potency but 5-BT is significantly less efficacious than sumatriptan. These data indicate that 5-BT is a relatively selective partial agonist at 5-HT1D receptors. 相似文献