全文获取类型
收费全文 | 1563篇 |
免费 | 122篇 |
出版年
2023年 | 7篇 |
2022年 | 15篇 |
2021年 | 16篇 |
2020年 | 24篇 |
2019年 | 21篇 |
2018年 | 21篇 |
2017年 | 24篇 |
2016年 | 38篇 |
2015年 | 57篇 |
2014年 | 74篇 |
2013年 | 96篇 |
2012年 | 118篇 |
2011年 | 118篇 |
2010年 | 85篇 |
2009年 | 47篇 |
2008年 | 82篇 |
2007年 | 83篇 |
2006年 | 94篇 |
2005年 | 78篇 |
2004年 | 80篇 |
2003年 | 60篇 |
2002年 | 65篇 |
2001年 | 23篇 |
2000年 | 16篇 |
1999年 | 17篇 |
1998年 | 17篇 |
1997年 | 11篇 |
1996年 | 11篇 |
1995年 | 14篇 |
1994年 | 17篇 |
1993年 | 10篇 |
1992年 | 15篇 |
1991年 | 16篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1975年 | 7篇 |
1971年 | 5篇 |
1969年 | 6篇 |
1968年 | 5篇 |
1967年 | 6篇 |
1881年 | 8篇 |
排序方式: 共有1685条查询结果,搜索用时 31 毫秒
91.
92.
93.
Maximilian C. Aichelburg Lukas Weseslindtner Mattias Mandorfer Robert Strassl Armin Rieger Thomas Reiberger Elisabeth Puchhammer-St?ckl Katharina Grabmeier-Pfistershammer 《PloS one》2015,10(8)
Background
Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects.Methods
Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months.Results
Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results.Conclusions
While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results. 相似文献94.
Arnaud P. J. Giese Jess G. Guarnaschelli Jonette A. Ward Daniel I. Choo Saima Riazuddin Zubair M. Ahmed 《PloS one》2015,10(11)
Radiotherapy of individuals suffering with head & neck or brain tumors subserve the risk of sensorineural hearing loss. Here, we evaluated the protective effect of Aminothiol PrC-210 (3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol) on the irradiated inner ear of guinea pigs. An intra-peritoneal or intra-tympanic dose of PrC-210 was administered prior to receiving a dose of gamma radiation (3000 cGy) to each ear. Auditory Brainstem Responses (ABRs) were recorded one week and two weeks after the radiation and compared with the sham animal group. ABR thresholds of guinea pigs that received an intra-peritoneal dose of PrC-210 were significantly better compared to the non-treated, control animals at one week post-radiation. Morphologic analysis of the inner ear revealed significant inflammation and degeneration of the spiral ganglion in the irradiated animals not treated with PrC-210. In contrast, when treated with PrC-210 the radiation effect and injury to the spiral ganglion was significantly alleviated. PrC-210 had no apparent cytotoxic effect in vivo and did not affect the morphology or count of cochlear hair cells. These findings suggest that aminothiol PrC-210 attenuated radiation-induced cochlea damage for at least one week and protected hearing. 相似文献
95.
Liquid films on shake flask walls explain increasing maximum oxygen transfer capacities with elevating viscosity 下载免费PDF全文
96.
Nora Wender Jan Hegermann Bettina Brunner Brigitte Nuscher Tim Bartels Armin Giese Klaus Beyer Stefan Eimer Konstanze F Winklhofer Christian Haass 《The EMBO journal》2010,29(20):3571-3589
Aggregation of α‐synuclein (αS) is involved in the pathogenesis of Parkinson's disease (PD) and a variety of related neurodegenerative disorders. The physiological function of αS is largely unknown. We demonstrate with in vitro vesicle fusion experiments that αS has an inhibitory function on membrane fusion. Upon increased expression in cultured cells and in Caenorhabditis elegans, αS binds to mitochondria and leads to mitochondrial fragmentation. In C. elegans age‐dependent fragmentation of mitochondria is enhanced and shifted to an earlier time point upon expression of exogenous αS. In contrast, siRNA‐mediated downregulation of αS results in elongated mitochondria in cell culture. αS can act independently of mitochondrial fusion and fission proteins in shifting the dynamic morphologic equilibrium of mitochondria towards reduced fusion. Upon cellular fusion, αS prevents fusion of differently labelled mitochondrial populations. Thus, αS inhibits fusion due to its unique membrane interaction. Finally, mitochondrial fragmentation induced by expression of αS is rescued by coexpression of PINK1, parkin or DJ‐1 but not the PD‐associated mutations PINK1 G309D and parkin Δ1–79 or by DJ‐1 C106A. 相似文献
97.
98.
Christoph Schmidt Klaus Höcherl Birgül Kurt Stefan Moritz Armin Kurtz Michael Bucher 《Cytokine》2010,49(1):30-38
In this prospective, randomized animal study, the role of proinflammatory cytokines in the pathogenesis sepsis-induced circulatory failure with downregulation of angiotensin-II-type-I-(AT1)-receptors was investigated. Sepsis in wild-type mice and in mice with deficiencies for TNF-α, IL-1β, IFN-γ or IL-6 was induced by cecal ligation and puncture (CLP) and wild-type mice were injected with cytokines. Animals were treated with glucocorticoids or small interfering RNA (siRNA) targeting single or multiple cytokines or NF-κB. Vascular smooth muscle cells (VSMCs) were incubated with cytokines. CLP resulted in circulatory failure and a significant downregulation of AT1-receptors. Injection of single proinflammatory cytokines also strongly downregulated AT1-receptors paralleled by a markedly endogenous liberation of further cytokines, whereas, simultaneous blockade of these endogenously activated cytokines by dexamethasone prevented downregulation of AT1-receptors. Furthermore, inhibition of multiple but not single cytokines by treatment with siRNA against multiple cytokines or NF-κB significantly attenuated CLP-induced AT1-receptor downregulation and prevented septic circulatory failure. Our data demonstrate that downregulation of AT1-receptors during sepsis is due to multiple but not single cytokines and define a relevant role for NF-κB in the pathogenesis of septic shock. 相似文献
99.
Since its discovery 10 years ago the histamine H(4) receptor (H(4)R) has attracted attention as a potential drug target, for instance, for the treatment of inflammatory and allergic diseases. Potent and selective ligands including agonists are required as pharmacological tools to study the role of the H(4)R in vitro and in vivo. Many H(4)R agonists, which were identified among already known histamine receptor ligands, show only low or insufficient H(4)R selectivity. In addition, the investigation of numerous H(4)R agonists in animal models is hampered by species-dependent discrepancies regarding potencies and histamine receptor selectivities of the available compounds, especially when comparing human and rodent receptors. This article gives an overview about structures, potencies, and selectivities of various compounds showing H(4)R agonistic activity and summarizes the structure-activity relationships of selected compound classes. 相似文献
100.
Ivane Abiatari Irene Esposito Tiago De Oliveira Klaus Felix Hong Xin Roland Penzel Thomas Giese Helmut Friess Jörg Kleeff 《Journal of cellular and molecular medicine》2010,14(5):1166-1179
Cell motility is controlled by the dynamic cytoskeleton and its related proteins, such as members of the ezrin/radixin/moesin (ERM) family, which act as signalling molecules inducing cytoskeleton remodelling. Although ERM proteins have been identified as important factors in various malignancies, functional redundancy between these proteins has hindered the dissection of their individual contribution. The aim of the present study was to analyse the functional role of moesin in pancreatic malignancies. Cancer cells of different malignant lesions of human and transgenic mice pancreata were evaluated by immunohistochemistry. For functional analysis, cell growth, adhesion and invasion assays were carried out after transient and stable knock‐down of moesin expression in pancreatic cancer cells. In vivo tumourigenicity was determined using orthotopic and metastatic mouse tumour models. We now show that moesin knock‐down increases migration, invasion and metastasis and influences extracellular matrix organization of pancreatic cancer. Moesin‐regulated migratory activities of pancreatic cancer cells were in part promoted through cellular translocation of β‐catenin, and re‐distribution and organization of the cytoskeleton. Analysis of human and different transgenic mouse pancreatic cancers demonstrated that moesin is a phenotypic marker for anaplastic carcinoma, suggesting that this ERM protein plays a specific role in pancreatic carcinogenesis. 相似文献