全文获取类型
收费全文 | 991篇 |
免费 | 132篇 |
出版年
2023年 | 5篇 |
2021年 | 9篇 |
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 15篇 |
2017年 | 14篇 |
2016年 | 20篇 |
2015年 | 37篇 |
2014年 | 28篇 |
2013年 | 54篇 |
2012年 | 58篇 |
2011年 | 50篇 |
2010年 | 36篇 |
2009年 | 36篇 |
2008年 | 55篇 |
2007年 | 47篇 |
2006年 | 41篇 |
2005年 | 43篇 |
2004年 | 56篇 |
2003年 | 45篇 |
2002年 | 39篇 |
2001年 | 24篇 |
2000年 | 35篇 |
1999年 | 19篇 |
1998年 | 27篇 |
1997年 | 12篇 |
1996年 | 16篇 |
1995年 | 13篇 |
1994年 | 20篇 |
1993年 | 10篇 |
1992年 | 15篇 |
1991年 | 13篇 |
1990年 | 27篇 |
1989年 | 12篇 |
1988年 | 16篇 |
1987年 | 5篇 |
1986年 | 17篇 |
1985年 | 23篇 |
1984年 | 18篇 |
1983年 | 10篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1969年 | 5篇 |
1938年 | 3篇 |
排序方式: 共有1123条查询结果,搜索用时 171 毫秒
101.
Menno Hoekstra Christian A.C. van der Lans Lars Gullestad Pål Aukrust Theo J.C. van Berkel Erik A.L. Biessen 《Biochemical and biophysical research communications》2010,394(3):792-797
Background
MicroRNAs are being used in the oncology field to characterize tumors and predict the survival of cancer patients. Here, we explored the potential of microRNAs as biomarkers for coronary artery disease (CAD) and acute coronary syndromes.Methods and results
Using real-time PCR-based profiling, we determined the microRNA signature of peripheral blood mononuclear cells (PBMCs) from stable and unstable CAD patients and unaffected controls. 129 of 157 microRNAs measured were expressed by PBMCs and low variability between separate PBMC pools was observed. The presence of CAD in general coincided with a marked 5-fold increase (P < 0.001) in the relative expression level of miR-135a, while the expression of miR-147 was 4-fold decreased (P < 0.05) in PBMCs from CAD patients as compared to controls, resulting in a 19-fold higher miR-135a/miR-147 ratio (P < 0.001) in CAD. MicroRNA/target gene/biological function linkage analysis suggested that the change in PBMC microRNA signature in CAD patients is probably associated with a change in intracellular cadherin/Wnt signaling. Interestingly, unstable angina pectoris patients could be discriminated from stable patients based upon their relatively high expression level of a cluster of three microRNAs including miR-134, miR-198, and miR-370, suggesting that the microRNA signatures can be used to identify patients at risk for acute coronary syndromes.Conclusions
The present study is the first to show that microRNA signatures can possibly be utilized to identify patients exhibiting atherosclerotic CAD in general and those at risk for acute coronary syndromes. Our findings highlight the importance of microRNAs signatures as novel tool to predict clinical disease outcomes. 相似文献102.
Microbial communities involved in anaerobic degradation of unsaturated or saturated long-chain fatty acids 总被引:1,自引:0,他引:1
Sousa DZ Pereira MA Stams AJ Alves MM Smidt H 《Applied and environmental microbiology》2007,73(4):1054-1064
Anaerobic long-chain fatty acid (LCFA)-degrading bacteria were identified by combining selective enrichment studies with molecular approaches. Two distinct enrichment cultures growing on unsaturated and saturated LCFAs were obtained by successive transfers in medium containing oleate and palmitate, respectively, as the sole carbon and energy sources. Changes in the microbial composition during enrichment were analyzed by denaturing gradient gel electrophoresis (DGGE) profiling of PCR-amplified 16S rRNA gene fragments. Prominent DGGE bands of the enrichment cultures were identified by 16S rRNA gene sequencing. A significant part of the retrieved 16S rRNA gene sequences was most similar to those of uncultured bacteria. Bacteria corresponding to predominant DGGE bands in oleate and palmitate enrichment cultures clustered with fatty acid-oxidizing bacteria within Syntrophomonadaceae and Syntrophobacteraceae families. A low methane yield, corresponding to 9 to 18% of the theoretical value, was observed in the oleate enrichment, and acetate, produced according to the expected stoichiometry, was not further converted to methane. In the palmitate enrichment culture, the acetate produced was completely mineralized and a methane yield of 48 to 70% was achieved from palmitate degradation. Furthermore, the oleate enrichment culture was able to use palmitate without detectable changes in the DGGE profile. However, the palmitate-specialized consortia degraded oleate only after a lag phase of 3 months, after which the DGGE profile had changed. Two predominant bands appeared, and sequence analysis showed affiliation with the Syntrophomonas genus. These bands were also present in the oleate enrichment culture, suggesting that these bacteria are directly involved in oleate degradation, emphasizing possible differences between the degradation of unsaturated and saturated LCFAs. 相似文献
103.
Non-viral vectors such as cationic lipids are capable of delivering nucleic acids, including genes, siRNA or antisense RNA
into cells, thus potentially resulting in their functional expression. These vectors are considered as an attractive alternative
for virus-based delivery systems, which may suffer from immunological and mutational hazards. However, the efficiency of cationic-mediated
gene delivery, although often sufficient for cell biological purposes, runs seriously short from a therapeutics point of view,
as realizing this objective requires a higher level of transfection than attained thus far. To develop strategies for improvement,
there is not so much a need for novel delivery systems. Rather, better insight is needed into the mechanism of delivery, including
lipoplex–cell surface interaction, route of internalization and concomitant escape of DNA/RNA into the cytosol, and transport
into the nucleus. Current work indicates that a major obstacle involves the relative inefficient destabilization of membrane-bounded
compartments in which lipoplexes reside after their internalization by the cell. Such an activity requires the capacity of
lipoplexes of undergoing polymorphic transitions such as a membrane destabilizing hexagonal phase, while cellular components
may aid in this process. A consequence of the latter notion is that for development of a novel generation of delivery devices,
entry pathways have to be triggered by specific targeting to select delivery into intracellular compartments which are most
susceptible to lipoplex-induced destabilization, thereby allowing the most efficient release of DNA, a minimal requirement
for optimizing non-viral vector-mediated transfection.
Dedicated to Prof. K. Arnold on the occasion of his 65th birthday. 相似文献
104.
Chitneni SK Deroose CM Fonge H Gijsbers R Dyubankova N Balzarini J Debyser Z Mortelmans L Verbruggen AM Bormans GM 《Bioorganic & medicinal chemistry letters》2007,17(12):3458-3462
An iodine-123 labeled bicyclic nucleoside analogue ([(123)I]-4) has been synthesized and evaluated as a potential single photon emission tomography (SPECT) reporter probe for the non-invasive imaging of expression of the varicella zoster virus thymidine kinase (VZV-tk) reporter gene. In vitro enzymatic assays revealed that the non-radioactive mono-iodo derivative 4 has good affinity for VZV-TK (IC(50): 4.2 microM). Biodistribution of [(123)I]-4 was examined in normal mice. Evaluation of [(123)I]-4 in HEK-293T cells showed 1.74-fold higher accumulation in VZV-TK-expressing cells compared to control cells. 相似文献
105.
Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88 总被引:1,自引:0,他引:1
Pel HJ de Winde JH Archer DB Dyer PS Hofmann G Schaap PJ Turner G de Vries RP Albang R Albermann K Andersen MR Bendtsen JD Benen JA van den Berg M Breestraat S Caddick MX Contreras R Cornell M Coutinho PM Danchin EG Debets AJ Dekker P van Dijck PW van Dijk A Dijkhuizen L Driessen AJ d'Enfert C Geysens S Goosen C Groot GS de Groot PW Guillemette T Henrissat B Herweijer M van den Hombergh JP van den Hondel CA van der Heijden RT van der Kaaij RM Klis FM Kools HJ Kubicek CP van Kuyk PA Lauber J 《Nature biotechnology》2007,25(2):221-231
106.
Cell polarity development and protein trafficking in hepatocytes lacking E-cadherin/beta-catenin-based adherens junctions
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Théard D Steiner M Kalicharan D Hoekstra D van Ijzendoorn SC 《Molecular biology of the cell》2007,18(6):2313-2321
Using a mutant hepatocyte cell line in which E-cadherin and beta-catenin are completely depleted from the cell surface, and, consequently, fail to form adherens junctions, we have investigated adherens junction requirement for apical-basolateral polarity development and polarized membrane trafficking. It is shown that these hepatocytes retain the capacity to form functional tight junctions, develop full apical-basolateral cell polarity, and assemble a subapical cortical F-actin network, although with a noted delay and a defect in subsequent apical lumen remodeling. Interestingly, whereas hepatocytes typically target the plasma membrane protein dipeptidyl peptidase IV first to the basolateral surface, followed by its transcytosis to the apical domain, hepatocytes lacking E-cadherin-based adherens junctions target dipeptidyl peptidase IV directly to the apical surface. Basolateral surface-directed transport of other proteins or lipids tested was not visibly affected in hepatocytes lacking E-cadherin-based adherens junctions. Together, our data show that E-cadherin/beta-catenin-based adherens junctions are dispensable for tight junction formation and apical lumen biogenesis but not for apical lumen remodeling. In addition, we suggest a possible requirement for E-cadherin/beta-catenin-based adherens junctions with regard to the indirect apical trafficking of specific proteins in hepatocytes. 相似文献
107.
Lawen A 《Molecular microbiology》2007,66(3):553-556
Involvement of the mitochondrial permeability transition pore (PTP) in apoptosis and PTP structure are highly controversial. In this issue of Molecular Microbiology, experiments based on yeast genetics analyse the roles of the three proteins commonly considered to form the PTP, i.e. porin, ADP/ATP carrier (ACC) and mitochondrial cyclophilin, on apoptosis-like cell death. Whereas knocking out cyclophilin had no effect, the porin-1 knockout yeast showed enhanced apoptosis, suggesting that porin-1 has an antiapoptotic role. Loss of the ACC proteins afforded protection against some causes of death, but enhanced death induced by H(2)O(2), suggesting a more complex role for the ACC proteins in regulating apoptosis-like death in yeast. 相似文献
108.
Annemarie MM Vlaar Angela EP Bouwmans Marinus JPG van Kroonenburgh Werner H Mess Selma C Tromp Piet GWM Wuisman Alfons GH Kessels Ania Winogrodzka Wim EJ Weber 《BMC neurology》2007,7(1):28
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD. 相似文献109.
Temperature-induced conformational transition of a model elastin-like peptide GVG(VPGVG)(3) in water 总被引:1,自引:0,他引:1
The conformation of a single elastin-like peptide GVG(VPGVG)3 in liquid water is studied by computer simulations in the temperature interval between 280 and 440 K. Two main conformational states of the peptide can be distinguished: a rigid conformational state, dominating at low temperatures, and a flexible conformational state, dominating at high temperatures. A temperature-induced transition between these states occurs at about 310 K, rather close to a transition temperature seen in experiments. This transition is accompanied by the thermal breaking of the hydrogen-bonded spanning network of the hydration water via a percolation transition upon heating. This finding indicates that the H-bond clustering structure of the hydration water plays an important role in the conformational stability of biomolecules. A second important observation is the Gaussian distribution of the end-to-end distance in the high-temperature state, which supports the idea of a rubber-like elasticity of the studied elastin-like peptide. Finally our results challenge the idea of the folding of elastin-like peptides upon heating. 相似文献
110.