全文获取类型
收费全文 | 516篇 |
免费 | 46篇 |
出版年
2023年 | 3篇 |
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 11篇 |
2019年 | 4篇 |
2018年 | 18篇 |
2017年 | 6篇 |
2016年 | 11篇 |
2015年 | 17篇 |
2014年 | 18篇 |
2013年 | 26篇 |
2012年 | 31篇 |
2011年 | 31篇 |
2010年 | 14篇 |
2009年 | 24篇 |
2008年 | 33篇 |
2007年 | 21篇 |
2006年 | 19篇 |
2005年 | 15篇 |
2004年 | 21篇 |
2003年 | 19篇 |
2002年 | 20篇 |
2001年 | 13篇 |
2000年 | 18篇 |
1999年 | 20篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 4篇 |
1986年 | 8篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1976年 | 2篇 |
1974年 | 6篇 |
1973年 | 2篇 |
1966年 | 2篇 |
1942年 | 2篇 |
1936年 | 2篇 |
排序方式: 共有562条查询结果,搜索用时 15 毫秒
91.
The intracellular, protozoan Theileria species parasites are the only eukaryotes known to transform another eukaryotic cell. One consequence of this parasite-dependent transformation is the acquisition of motile and invasive properties of parasitized cells in vitro and their metastatic dissemination in the animal, which causes East Coast Fever (T. parva) or Tropical Theileriosis (T. annulata). These motile and invasive properties of infected host cells are enabled by parasite-dependent, poorly understood F-actin dynamics that control host cell membrane protrusions. Herein, we dissected functional and structural alterations that cause acquired motility and invasiveness of T. annulata-infected cells, to understand the molecular basis driving cell dissemination in Tropical Theileriosis. We found that chronic induction of TNFα by the parasite contributes to motility and invasiveness of parasitized host cells. We show that TNFα does so by specifically targeting expression and function of the host proto-oncogenic ser/thr kinase MAP4K4. Blocking either TNFα secretion or MAP4K4 expression dampens the formation of polar, F-actin-rich invasion structures and impairs cell motility in 3D. We identified the F-actin binding ERM family proteins as MAP4K4 downstream effectors in this process because TNFα-induced ERM activation and cell invasiveness are sensitive to MAP4K4 depletion. MAP4K4 expression in infected cells is induced by TNFα-JNK signalling and maintained by the inhibition of translational repression, whereby both effects are parasite dependent. Thus, parasite-induced TNFα promotes invasive motility of infected cells through the activation of MAP4K4, an evolutionary conserved kinase that controls cytoskeleton dynamics and cell motility. Hence, MAP4K4 couples inflammatory signaling to morphodynamic processes and cell motility, a process exploited by the intracellular Theileria parasite to increase its host cell''s dissemination capabilities. 相似文献
92.
Chuan-Ming Xie Xiao-Yu Liu Kathy WY Sham Josie MY Lai Christopher HK Cheng 《Autophagy》2014,10(9):1495-1508
EEF2K (eukaryotic elongation factor-2 kinase), also known as Ca2+/calmodulin-dependent protein kinase III, functions in downregulating peptide chain elongation through inactivation of EEF2 (eukaryotic translation elongation factor 2). Currently, there is a limited amount of information on the promotion of autophagic survival by EEF2K in breast and glioblastoma cell lines. However, the precise role of EEF2K in carcinogenesis as well as the underlying mechanism involved is still poorly understood. In this study, contrary to the reported autophagy-promoting activity of EEF2K in certain cancer cells, EEF2K is shown to negatively regulate autophagy in human colon cancer cells as indicated by the increase of LC3-II levels, the accumulation of LC3 dots per cell, and the promotion of autophagic flux in EEF2K knockdown cells. EEF2K negatively regulates cell viability, clonogenicity, cell proliferation, and cell size in colon cancer cells. Autophagy induced by EEF2K silencing promotes cell survival and does not potentiate the anticancer efficacy of the AKT inhibitor MK-2206. In addition, autophagy induced by silencing of EEF2K is attributed to induction of protein synthesis and activation of the AMPK-ULK1 pathway, independent of the suppression of MTOR activity and ROS generation. Knockdown of AMPK or ULK1 significantly abrogates EEF2K silencing-induced increase of LC3-II levels, accumulation of LC3 dots per cell as well as cell proliferation in colon cancer cells. In conclusion, silencing of EEF2K promotes autophagic survival via activation of the AMPK-ULK1 pathway in colon cancer cells. This finding suggests that upregulation of EEF2K activity may constitute a novel approach for the treatment of human colon cancer. 相似文献
93.
94.
Stephanie Seah Abu Bakar Ali Asad Richard Baumgartner Dai Feng Donald S. Williams Elaine Manigbas John D. Beaver Torsten Reese Brian Henry Jeffrey L. Evelhoch Chih-Liang Chin 《PloS one》2014,9(10)
Background
Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP). Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored.Methodology
We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV)-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v.), a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC) values from brain areas with high density of µ-opioid receptors.Principal Findings
In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, p<0.05, n = 4). This observation is strikingly consistent with µ-opioid receptor distribution depicted by [6-O-[11C]methyl]buprenorphine ([11C]BPN) positron emission tomography imaging study in baboons. Furthermore, our findings are consistent with previous buprenorphine phMRI studies in humans and conscious rats which collectively demonstrate the cross-species translatability of awake imaging. Conversely, no significant change in activated brain regions was found in the same animals imaged under the anesthetized condition.Conclusions
Our data highlight the utility and importance of awake NHP imaging as a translational imaging biomarker for drug research. 相似文献95.
96.
Conrad J. Baumgartner 《The Western journal of medicine》1950,73(6):466-472
The embryonic origin of lateral cysts and fistulas remains controversial. They are, however, located in the general anatomic pattern of the embryonic thymic duct, which starts in the lateral pharyngeal wall and passes under the sternomastoid muscle to enter the mediastinum. The cyst is a unilocular, semiattached, non-translucent mass which has a tendency to become infected in 30 per cent of cases.The preauricular sinus occurs in front of the ear and is due either to a branchial cleft or an inclusion of one of the six primitive buds which form the external ear.Cystic hygroma is due to sequestrated lymphatic channels. These are always multilocular and rather invasive and may extend into mediastinum and arms.Diagnosis and treatment are considered in this presentation. 相似文献
97.
W. J. Baumgartner 《Cell and tissue research》1929,9(4):603-639
Ohne Zusammenfassung
Mit 3 Textabbildungen und Tafel IX–XI 相似文献
98.
Andreas Baumgartner Luis Hiedra Graziano Pinna Murat Eravci Hans Prengel Harald Meinhold 《Journal of neurochemistry》1998,71(2):817-826
Abstract: The effects of different kinds of acute stressor on thyroid hormone concentrations and deiodinase activities were investigated in four brain regions (frontal cortex, amygdala, hypothalamus, and cerebellum) and in the pituitaries and livers of adult male rats. Five groups of rats were killed after each of the following stressors: (a) an intraperitoneal injection of saline, (b) intragastric intubation, (c) and (d) two different forms of handling, being grasped as for intraperitoneal injection and being moved from one cage to another, and (e) a 2-h period spent in a slowly rotating drum. Two other groups were placed in the rotating drums for 10 and 19 h (sleep deprivation experiment), respectively. All stressors induced significant (in some cases up to 200%) increases in the activity of type II 5′-iodothyronine deiodinase, which catalyzes the deiodination of the prohormone l -thyroxine (T4) to the active metabolite 3,3′,5-triiodo-l -thyronine (T3). As a consequence, the tissue concentrations of T4 fell, and those of T3 rose (sometimes by up to 300%). However, these changes were limited to selected areas of the brain that were specific for each stressor and were not seen in all brain regions investigated in any group. No clear-cut effects of stress were seen on the activities of the type III 5-iodothyronine deiodinase isoenzyme, which catalyzes the inactivation of T3, on liver or serum thyroid hormone concentrations or on liver of brain type I 5′-iodothyronine deiodinase activities. In summary, our results show that even mild and very brief stress can induce marked increases in T3 concentrations specifically in brain but not in liver or blood. Thus, contrary to common opinion, thyroid hormones may play an important physiological role in stress reactions, at least in tissues that contain type II 5′-iodothyronine deiodinase, such as brain and pituitary. 相似文献
99.
Kyle Nash Bastian Schiller Lorena R. R. Gianotti Thomas Baumgartner Daria Knoch 《PloS one》2013,8(11)
Recent research demonstrates that response inhibition—a core executive function—may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test). Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes—two established electrophysiological indices of response inhibition—both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes. 相似文献
100.
Rapid detection of viable Legionella pneumophila in tap water by a qPCR and RT‐PCR‐based method
下载免费PDF全文
![点击此处可从《Journal of applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R. Boss A. Baumgartner S. Kroos M. Blattner R. Fretz D. Moor 《Journal of applied microbiology》2018,125(4):1216-1225