全文获取类型
收费全文 | 1361篇 |
免费 | 168篇 |
国内免费 | 1篇 |
出版年
2022年 | 14篇 |
2021年 | 15篇 |
2020年 | 13篇 |
2019年 | 13篇 |
2018年 | 17篇 |
2017年 | 24篇 |
2016年 | 22篇 |
2015年 | 49篇 |
2014年 | 61篇 |
2013年 | 67篇 |
2012年 | 88篇 |
2011年 | 80篇 |
2010年 | 52篇 |
2009年 | 48篇 |
2008年 | 65篇 |
2007年 | 31篇 |
2006年 | 50篇 |
2005年 | 37篇 |
2004年 | 41篇 |
2003年 | 50篇 |
2002年 | 36篇 |
2001年 | 47篇 |
2000年 | 52篇 |
1999年 | 44篇 |
1998年 | 12篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 25篇 |
1994年 | 20篇 |
1993年 | 22篇 |
1992年 | 35篇 |
1991年 | 26篇 |
1990年 | 32篇 |
1989年 | 25篇 |
1988年 | 36篇 |
1987年 | 27篇 |
1986年 | 21篇 |
1985年 | 29篇 |
1984年 | 18篇 |
1983年 | 14篇 |
1982年 | 10篇 |
1979年 | 17篇 |
1978年 | 10篇 |
1975年 | 7篇 |
1974年 | 11篇 |
1973年 | 12篇 |
1972年 | 11篇 |
1971年 | 7篇 |
1969年 | 7篇 |
1967年 | 7篇 |
排序方式: 共有1530条查询结果,搜索用时 15 毫秒
91.
S?ren Franzenburg Sebastian Fraune Philipp M Altrock Sven Künzel John F Baines Arne Traulsen Thomas CG Bosch 《The ISME journal》2013,7(4):781-790
Animals are colonized by complex bacterial communities. The processes controlling community membership and influencing the establishment of the microbial ecosystem during development are poorly understood. Here we aimed to explore the assembly of bacterial communities in Hydra with the broader goal of elucidating the general rules that determine the temporal progression of bacterial colonization of animal epithelia. We profiled the microbial communities in polyps at various time points after hatching in four replicates. The composition and temporal patterns of the bacterial communities were strikingly similar in all replicates. Distinct features included high diversity of community profiles in the first week, a remarkable but transient adult-like profile 2 weeks after hatching, followed by progressive emergence of a stable adult-like pattern characterized by low species diversity and the preponderance of the Betaproteobacterium Curvibacter. Intriguingly, this process displayed important parallels to the assembly of human fecal communities after birth. In addition, a mathematical modeling approach was used to uncover the organizational principles of this colonization process, suggesting that both, local environmental or host-derived factor(s) modulating the colonization rate, as well as frequency-dependent interactions of individual bacterial community members are important aspects in the emergence of a stable bacterial community at the end of development. 相似文献
92.
Maria A. Hegeman Marije P. Hennus Pieter M. Cobelens Annemieke Kavelaars Nicolaas J. G. Jansen Marcus J. Schultz Adrianus J. van Vught Cobi J. Heijnen 《PloS one》2013,8(2)
Background
Ventilator–induced lung injury (VILI) is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF) has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar–capillary barrier dysfunction in an established murine model of VILI.Methods
Healthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O (“lower” tidal volumes of ∼7.5 ml/kg; LVT) or 18 cmH2O (“higher” tidal volumes of ∼15 ml/kg; HVT). Dexamethasone was intravenously administered at the initiation of HVT–ventilation. Non–ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios.Results
Particularly HVT–ventilation led to alveolar–capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro–inflammatory response in lungs of HVT–ventilated mice, without improving alveolar–capillary permeability, gas exchange and pulmonary edema formation.Conclusions
Dexamethasone treatment completely abolishes ventilator–induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar–capillary barrier dysfunction in an established murine model of VILI. 相似文献93.
Oliver G. Bosch Michael Wagner Frank Jessen Kai-Uwe Kühn Alexius Joe Erich Seifritz Wolfgang Maier Hans-Jürgen Biersack Boris B. Quednow 《PloS one》2013,8(4)
Introduction
3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users.Methods
Brain glucose metabolism in rest was assessed using 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. 18FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test.Results
As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex.Conclusions
Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined fronto-parieto-mediotemporal dysfunction. 相似文献94.
Yoshihisa Shimizu Chiaki Yoshikawa Junji Suzuki Jun Qiu Edith van den Bosch 《Biotechnology letters》2016,38(3):403-408
Objective
When polymer brushes are applied as the inner coating for artificial blood vessels, they may induce unwanted responses in vascular endothelial cells continuously exposed to the polymer surface. Accordingly, we have examined the in vitro effect of non-biofouling concentrated polymer brushes (CPBs) on pro-inflammatory and angiogenic responses of human umbilical vein endothelial cells (HUVECs).Results
Micro-patterned CPBs were prepared on silicon wafers using biocompatible polymers, poly(poly(ethylene glycol)methyl ether methacrylate) (PPEGMA) and poly(2-hydroxyethyl methacrylate) (PHEMA). HUVECs were cultured on PPEGMA-CPBs and PHEMA-CPBs with different channel widths (20, 50, and 80 µm) and analyzed for mRNA expression of the pro-inflammatory cytokines IL-6 and IL-8 and angiogeneic vascular endothelial growth factor (VEGF). Irrespective of channel width, PHEMA-CPBs reduced the expression of all target genes, whereas PPEGMA-CPBs reduced VEGF and did not affect IL-6 and IL-8 levels.Conclusion
Micro-patterned CPBs, irrespective of chemical structure or adhesion area, do not induce the expression of important pro-inflammatory and angiogenic mediators in endothelial cells.95.
Nicky HGM Peters Inne HM Borel Rinkes Willem PTM Mali Maurice AAJ van den Bosch Remmert K Storm Peter W Plaisier Erwin de Boer Adriaan J van Overbeeke Petra HM Peeters 《Trials》2007,8(1):1-7
Background
In orthodontic treatment, anchorage control is a fundamental aspect. Usually conventional mechanism for orthodontic anchorage control can be either extraoral or intraoral that is headgear or intermaxillary elastics. Their use are combined with various side effects such as tipping of occlusal plane or undesirable movements of teeth. Especially in cases, where key-teeth are missing, conventional anchorage defined as tooth-borne anchorage will meet limitations. Therefore, the use of endosseous implants for anchorage purposes are increasingly used to achieve positional stability and maximum anchorage.Methods/Design
The intended study is designed as a prospective, multicenter randomized controlled trial (RCT), comparing and contrasting the effect of early loading of palatal implant therapy versus implant loading after 12 weeks post implantation using the new ortho-implant type II anchor system device (Orthosystem Straumann, Basel, Switzerland). 124 participants, mainly adult males or females, whose diagnoses require temporary stationary implant-based anchorage treatment will be randomized 1:1 to one of two treatment groups: group 1 will receive a loading of implant standard therapy after a healing period of 12 week (gold standard), whereas group 2 will receive an early loading of orthodontic implants within 1 week after implant insertion. Participants will be at least followed for 12 months after implant placement. The primary endpoint is to investigate the behavior of early loaded palatal implants in order to find out if shorter healing periods might be justified to accelerate active orthodontic treatment. Secondary outcomes will focus e.g. on achievement of orthodontic treatment goals and quantity of direct implant-bone interface of removed bone specimens. As tertiary objective, a histologic and microtomography evaluation of all retrieved implants will be performed to obtain data on the performance of the SLA surface in human bone evaluation of all retrieved implants. Additionally, resonance frequency analysis (RFA, Osstell? mentor) will be used at different times for clinically monitoring the implant stability and for histological comparison in order to measure the reliability of the resonance frequency measuring device.Trial registration
Current Controlled Trials ISRCTN97142521. 相似文献96.
Bosch L Sanz ML Montilla A Alegría A Farré R del Castillo MD 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,860(1):69-77
Protein quality was assayed by simultaneous measurement of lysine (Lys), carboxymethyllysine (CML) and lysinoalanine (LAL). GC-FID analysis of N-tert-butyl dimethylsilyl (tBDMSi) derivatives of these amino acids was undertaken. tBDMSi derivates were separated on a CP-SIL 5CB commercially fused silica capillary column (25 m x 0.25 mm i.d., 0.25 microm film thickness) employing a thermal gradient programmed from 200 to 300 degrees C. The identity of tBDMSi derivatives of Lys, CML and LAL was established by GC-MS while FID detection was employed for quantification. Analytical parameters such as linearity (lysine 350-4200 microM, LAL 3-81 microM, CML 16-172 microM), precision (1-13% variation coefficients), accuracy (85-108% average recovery) and limits of detection (lysine 0.4 mg/100 g protein, LAL 5.0 mg/100 g protein, CML 3.4 mg/100 g protein) and quantification (lysine 1.4 mg/100g protein, LAL 15.2 mg/100 g protein, CML 11.2 mg/100 g protein) were determined for validation of the analytical approach. Model systems and real foods have been studied. Kinetic of CML formation from different food proteins (BSA, soy protein, casein and gluten) was performed employing model systems. Carboxymethylation rate depended on the source of protein. Maillard reaction progressed to advanced stages damaging the protein quality of stored infant foods, soy drinks, boiled eggs and dry powdered crepes. CML values ranged from 62 to 440 mg/100 g protein were measured. LAL was also formed during boiling eggs (21-68 mg/100g protein) indicating additional damage by crosslinking reaction. In agreement, lysine content was affected by both food processing and storage. 相似文献
97.
Ga Hun Boo Ying‐Xiong Qiu Jung Yeon Kim Put O. Ang Samuel Bosch Olivier De Clerck Peimin He Atsushi Higa Bangqin Huang Kazuhiro Kogame Shao‐Lun Liu Tu van Nguyen Shoichiro Suda Ryuta Terada Kathy Ann Miller Sung Min Boo 《Journal of phycology》2019,55(6):1319-1334
The evolutionary and population demographic history of marine red algae in East Asia is poorly understood. Here, we reconstructed the phylogeographies of two upper intertidal species endemic to East Asia, Gelidiophycus divaricatus and G. freshwateri. Phylogenetic and phylogeographic inferences of 393 mitochondrial cox1, 128 plastid rbcL, and 342 nuclear ITS2 sequences were complemented with ecological niche models. Gelidiophycus divaricatus, a southern species adapted to warm water, is characterized by a high genetic diversity and a strong geographical population structure, characteristic of stable population sizes and sudden reduction to recent expansion. In contrast, G. freshwateri, a northern species adapted to cold temperate conditions, is genetically relatively homogeneous with a shallow population structure resulting from steady population growth and recent equilibrium. The overlap zone of the two species roughly matches summer and winter isotherms, indicating that surface seawater temperature is a key feature influencing species range. Unidirectional genetic introgression was detected at two sites on Jeju Island where G. divaricatus was rare while G. freshwateri was common, suggesting the occurrence of asymmetric natural hybrids, a rarely reported event for rhodophytes. Our results illustrate that Quaternary climate oscillations have left strong imprints on the current day genetic structure and highlight the importance of seawater temperature and sea level change in driving speciation in upper intertidal seaweed species. 相似文献
98.
Anne Mouré Elodie Bacou Steffi Bosch Dominique Jegou Apolline Salama David Riochet Olivier Gauthier Gilles Blancho Jean-Paul Soulillou Denis Poncelet Eric Olmos Jean-Marie Bach Mathilde Mosser 《Biotechnology and bioengineering》2019,116(5):1176-1189
The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O2 supply after transplantation remains a major challenge. In this study, we address the O2 limitation by combining silicone-encapsulated CaO2 (silicone-CaO2) to generate O2 with an extracellular hemoglobin O2-carrier coencapsulated with islets. We showed that the hemoglobin improved by 37% the O2-diffusivity through an alginate hydrogel and displayed antioxidant properties neutralizing deleterious reactive O2 species produced by silicone-CaO2. While the hemoglobin alone failed to maintain alginate macroencapsulated neonate pig islets under hypoxia, silicone-CaO2 alone or combined to the hemoglobin restored islet viability and insulin secretion and prevented proinflammatory metabolism (PTGS2 expression). Interestingly, the combination took the advantages of the two individual strategies, improved neonate pig islet viability and insulin secretion in normoxia, and VEGF secretion and PDK1 normalization in hypoxia. Moreover, we confirmed the specific benefits of the combination compared to silicone-CaO2 alone on murine pseudo-islet viability in normoxia and hypoxia. For the first time, our results show the interest of combining an O2 provider with hemoglobin as an effective strategy to overcome O2 limitations in tissue engineering. 相似文献
99.
J. RoigSoriano C. GrinFerr J. F. EspinosaParrilla C. R. Abraham A. Bosch M. Palls Miguel Chilln 《Aging cell》2022,21(4)
Senescence represents a stage in life associated with elevated incidence of morbidity and increased risk of mortality due to the accumulation of molecular alterations and tissue dysfunction, promoting a decrease in the organism''s protective systems. Thus, aging presents molecular and biological hallmarks, which include chronic inflammation, epigenetic alterations, neuronal dysfunction, and worsening of physical status. In this context, we explored the AAV9‐mediated expression of the two main isoforms of the aging‐protective factor Klotho (KL) as a strategy to prevent these general age‐related features using the senescence‐accelerated mouse prone 8 (SAMP8) model. Both secreted and transmembrane KL isoforms improved cognitive performance, physical state parameters, and different molecular variables associated with aging. Epigenetic landscape was recovered for the analyzed global markers DNA methylation (5‐mC), hydroxymethylation (5‐hmC), and restoration occurred in the acetylation levels of H3 and H4. Gene expression of pro‐ and anti‐inflammatory mediators in central nervous system such as TNF‐α and IL‐10, respectively, had improved levels, which were comparable to the senescence‐accelerated‐mouse resistant 1 (SAMR1) healthy control. Additionally, this improvement in neuroinflammation was supported by changes in the histological markers Iba1, GFAP, and SA β‐gal. Furthermore, bone tissue structural variables, especially altered during senescence, recovered in SAMP8 mice to SAMR1 control values after treatment with both KL isoforms. This work presents evidence of the beneficial pleiotropic role of Klotho as an anti‐aging therapy as well as new specific functions of the KL isoforms for the epigenetic regulation and aged bone structure alteration in an aging mouse model. 相似文献
100.