全文获取类型
收费全文 | 4986篇 |
免费 | 344篇 |
国内免费 | 1篇 |
出版年
2023年 | 34篇 |
2022年 | 73篇 |
2021年 | 121篇 |
2020年 | 88篇 |
2019年 | 104篇 |
2018年 | 117篇 |
2017年 | 100篇 |
2016年 | 173篇 |
2015年 | 263篇 |
2014年 | 292篇 |
2013年 | 379篇 |
2012年 | 458篇 |
2011年 | 385篇 |
2010年 | 268篇 |
2009年 | 232篇 |
2008年 | 318篇 |
2007年 | 305篇 |
2006年 | 273篇 |
2005年 | 235篇 |
2004年 | 197篇 |
2003年 | 203篇 |
2002年 | 165篇 |
2001年 | 44篇 |
2000年 | 45篇 |
1999年 | 45篇 |
1998年 | 28篇 |
1997年 | 27篇 |
1996年 | 34篇 |
1995年 | 30篇 |
1994年 | 23篇 |
1993年 | 25篇 |
1992年 | 30篇 |
1991年 | 25篇 |
1990年 | 20篇 |
1989年 | 19篇 |
1988年 | 16篇 |
1987年 | 11篇 |
1986年 | 14篇 |
1985年 | 14篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1981年 | 6篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1978年 | 10篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 8篇 |
排序方式: 共有5331条查询结果,搜索用时 15 毫秒
131.
Florence Miller Hervé Lécuyer Olivier Join‐Lambert Sandrine Bourdoulous Stefano Marullo Xavier Nassif Mathieu Coureuil 《Cellular microbiology》2013,15(4):512-519
The brain and meningeal spaces are protected from bacterial invasion by the blood–brain barrier, formed by specialized endothelial cells and tight intercellular junctional complexes. However, once in the bloodstream, Neisseria meningitidis crosses this barrier in about 60% of the cases. This highlights the particular efficacy with which N. meningitidis targets the brain vascular cell wall. The first step of central nervous system invasion is the direct interaction between bacteria and endothelial cells. This step is mediated by the type IV pili, which induce a remodelling of the endothelial monolayer, leading to the opening of the intercellular space. In this review, strategies used by the bacteria to survive in the bloodstream, to colonize the brain vasculature and to cross the blood–brain barrier will be discussed. 相似文献
132.
Tania Gioia Giuseppina Logozzo Giovanna Attene Elisa Bellucci Stefano Benedettelli Valeria Negri Roberto Papa Pierluigi Spagnoletti Zeuli 《PloS one》2013,8(10)
Common bean diversity within and between Mesoamerican and Andean gene pools was compared in 89 landraces from America and 256 landraces from Europe, to elucidate the effects of bottleneck of introduction and selection for adaptation during the expansion of common bean (Phaseolus vulgaris L.) in Europe. Thirteen highly polymorphic nuclear microsatellite markers (nuSSRs) were used to complement chloroplast microsatellite (cpSSRs) and nuclear markers (phaseolin and Pv-shatterproof1) data from previous studies. To verify the extent of the introduction bottleneck, inter-gene pool hybrids were distinguished from “pure” accessions. Hybrids were identified on the basis of recombination of gene pool specific cpSSR, phaseolin and Pv-shatterproof1 markers with a Bayesian assignments based on nuSSRs, and with STRUCTURE admixture analysis. More hybrids were detected than previously, and their frequency was almost four times larger in Europe (40.2%) than in America (12.3%). The genetic bottleneck following the introduction into Europe was not evidenced in the analysis including all the accessions, but it was significant when estimated only with “pure” accessions, and five times larger for Mesoamerican than for Andean germplasm. The extensive inter-gene pool hybridization generated a large amount of genotypic diversity that mitigated the effects of the bottleneck that occurred when common bean was introduced in Europe. The implication for evolution and the advantages for common bean breeding are discussed. 相似文献
133.
Alessandro Ghezzo Paola Visconti Provvidenza M. Abruzzo Alessandra Bolotta Carla Ferreri Giuseppe Gobbi Gemma Malisardi Stefano Manfredini Marina Marini Laura Nanetti Emanuela Pipitone Francesca Raffaelli Federica Resca Arianna Vignini Laura Mazzanti 《PloS one》2013,8(6)
It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (−66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD. 相似文献
134.
135.
Stefano Da Sacco Kevin V. Lemley Sargis Sedrakyan Ilenia Zanusso Astgik Petrosyan Janos Peti-Peterdi James Burford Roger E. De Filippo Laura Perin 《PloS one》2013,8(12)
Amniotic fluid is in continuity with multiple developing organ systems, including the kidney. Committed, but still stem-like cells from these organs may thus appear in amniotic fluid. We report having established for the first time a stem-like cell population derived from human amniotic fluid and possessing characteristics of podocyte precursors. Using a method of triple positive selection we obtained a population of cells (hAKPC-P) that can be propagated in vitro for many passages without immortalization or genetic manipulation. Under specific culture conditions, these cells can be differentiated to mature podocytes. In this work we compared these cells with conditionally immortalized podocytes, the current gold standard for in vitro studies. After in vitro differentiation, both cell lines have similar expression of the major podocyte proteins, such as nephrin and type IV collagen, that are characteristic of mature functional podocytes. In addition, differentiated hAKPC-P respond to angiotensin II and the podocyte toxin, puromycin aminonucleoside, in a way typical of podocytes. In contrast to immortalized cells, hAKPC-P have a more nearly normal cell cycle regulation and a pronounced developmental pattern of specific protein expression, suggesting their suitability for studies of podocyte development for the first time in vitro. These novel progenitor cells appear to have several distinct advantages for studies of podocyte cell biology and potentially for translational therapies. 相似文献
136.
Protected areas are increasingly considered to play a key role in the global maintenance of ecosystem processes and the ecosystem services they provide. It is thus vital to assess the extent to which existing protected area systems represent those services. Here, for the first time, we document the effectiveness of the current Chilean protected area system and its planned extensions in representing both ecosystem services (plant productivity, carbon storage and agricultural production) and biodiversity. Additionally, we evaluate the effectiveness of protected areas based on their respective management objectives. Our results show that existing protected areas in Chile do not contain an unusually high proportion of carbon storage (14.9%), agricultural production (0.2%) or biodiversity (11.8%), and also represent a low level of plant productivity (Normalized Difference Vegetation Index of 0.38). Proposed additional priority sites enhance the representation of ecosystem services and biodiversity, but not sufficiently to attain levels of representation higher than would be expected for their area of coverage. Moreover, when the species groups were assessed separately, amphibians was the only one well represented. Suggested priority sites for biodiversity conservation, without formal protection yet, was the only protected area category that over-represents carbon storage, agricultural production and biodiversity. The low representation of ecosystem services and species’ distribution ranges by the current protected area system is because these protected areas are heavily biased toward southern Chile, and contain large extents of ice and bare rock. The designation and management of proposed priority sites needs to be addressed in order to increase the representation of ecosystem services within the Chilean protected area system. 相似文献
137.
Tullio Palmerini Luciana Tomasi Chiara Barozzi Diego Della Riva Andrea Mariani Nevio Taglieri Ornella Leone Claudio Ceccarelli Stefano De Servi Angelo Branzi Philippe Genereux Gregg W. Stone Jasimuddin Ahamed 《PloS one》2013,8(12)
Introduction
Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention.Methods
Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients.Results
Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p<0.001). Tissue factor was also identified by immunoprecipitation in 10 patients, with significant variability among band intensities.Conclusions
Active tissue factor is present in coronary artery thrombi of patients with ST-segment elevation acute myocardial infarction, suggesting that it contributes to activate the coagulation cascade ensuing in coronary thrombosis. 相似文献138.
Expectation contributes to placebo and nocebo responses in Parkinson''s disease (PD). While there is evidence for expectation-induced modulations of bradykinesia, little is known about the impact of expectation on resting tremor. Subthalamic nucleus (STN) deep brain stimulation (DBS) improves cardinal PD motor symptoms including tremor whereas impairment of verbal fluency (VF) has been observed as a potential side-effect. Here we investigated how expectation modulates the effect of STN-DBS on resting tremor and its interaction with VF. In a within-subject-design, expectation of 24 tremor-dominant PD patients regarding the impact of STN-DBS on motor symptoms was manipulated by verbal suggestions (positive [placebo], negative [nocebo], neutral [control]). Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Resting tremor was recorded by accelerometry and bradykinesia of finger tapping and diadochokinesia were assessed by a 3D ultrasound motion detection system. VF was quantified by lexical and semantic tests. In a subgroup of patients, the effect of STN-DBS on tremor was modulated by expectation, i.e. tremor decreased (placebo response) or increased (nocebo response) by at least 10% as compared to the control condition while no significant effect was observed for the overall group. Interestingly, nocebo responders in MedON were additionally characterized by significant impairment in semantic verbal fluency. In contrast, bradykinesia was not affected by expectation. These results indicate that the therapeutic effect of STN-DBS on tremor can be modulated by expectation in a subgroup of patients and suggests that tremor is also among the parkinsonian symptoms responsive to placebo and nocebo interventions. While positive expectations enhanced the effect of STN-DBS by further decreasing the magnitude of tremor, negative expectations counteracted the therapeutic effect and at the same time exacerbated a side-effect often associated with STN-DBS. The present findings underscore the potency of patients'' expectation and its relevance for therapeutic outcomes. 相似文献
139.
Stefano Lepore Helmar Waiczies Jan Hentschel Yiyi Ji Julia Skodowski Andreas Pohlmann Jason M. Millward Friedemann Paul Jens Wuerfel Thoralf Niendorf Sonia Waiczies 《PloS one》2013,8(8)
Inflammatory disorders of the central nervous system such as multiple sclerosis and acute disseminated encephalomyelitis involve an invasion of immune cells that ultimately leads to white matter demyelination, neurodegeneration and development of neurological symptoms. A clinical diagnosis is often made when neurodegenerative processes are already ongoing. In an attempt to seek early indicators of disease, we studied the temporal and spatial distribution of brain modifications in experimental autoimmune encephalomyelitis (EAE). In a thorough magnetic resonance imaging study performed with EAE mice, we observed significant enlargement of the ventricles prior to disease clinical manifestation and an increase in free water content within the cerebrospinal fluid as demonstrated by changes in T2 relaxation times. The increase in ventricle size was seen in the lateral, third and fourth ventricles. In some EAE mice the ventricle size started returning to normal values during disease remission. In parallel to this macroscopic phenomenon, we studied the temporal evolution of microscopic lesions commonly observed in the cerebellum also starting prior to disease onset. Our data suggest that changes in ventricle size during the early stages of brain inflammation could be an early indicator of the events preceding neurological disease and warrant further exploration in preclinical and clinical studies. 相似文献
140.
Laercio Martins De Stefano Alex Lombardi Barbosa Ferraz Ana Lúcia dos Anjos Ferreira Ana Lúcia Gut Ana Lúcia Cogni Elaine Farah Beatriz Bojikian Matsubara 《PloS one》2013,8(10)