全文获取类型
收费全文 | 484篇 |
免费 | 30篇 |
专业分类
514篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 9篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 13篇 |
2015年 | 24篇 |
2014年 | 23篇 |
2013年 | 28篇 |
2012年 | 27篇 |
2011年 | 24篇 |
2010年 | 13篇 |
2009年 | 17篇 |
2008年 | 33篇 |
2007年 | 25篇 |
2006年 | 24篇 |
2005年 | 27篇 |
2004年 | 26篇 |
2003年 | 25篇 |
2002年 | 23篇 |
2001年 | 5篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1993年 | 4篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 6篇 |
1982年 | 4篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1970年 | 5篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1965年 | 2篇 |
1960年 | 2篇 |
1959年 | 2篇 |
1936年 | 2篇 |
1933年 | 2篇 |
排序方式: 共有514条查询结果,搜索用时 15 毫秒
21.
Pedro A. Sosa Edna A. González‐González Miguel A. González‐Pérez Pedro Luis Pérez de Paz 《Botanical journal of the Linnean Society. Linnean Society of London》2013,173(2):258-268
Islands offer an interesting framework in which to study the effect of geographical isolation on population genetic differentiation. For plant species with high dispersal abilities, however, oceanic barriers may not represent a factor promoting strong population structure. In this work, we analysed seven nuclear microsatellite loci in Ilex (Aquifoliaceae), a bird‐dispersed plant group, to infer patterns of genetic differentiation among Macaronesian taxa: I. canariensis, I. perado ssp. lopezlilloi, I. perado ssp. platyphylla (Canary Islands) and I. perado ssp. azorica (Azores). In agreement with current taxonomic classification, our results revealed a high genetic differentiation between Ilex lineages (I. canariensis and the I. perado complex), and also supported previous hypotheses that these are the result of independent dispersal events to the islands. In contrast, genetic differentiation between I. perado ssp. azorica and the two subspecies from the Canaries was high, suggesting that taxonomic revision may be necessary. Levels of genetic variation at microsatellite loci in ssp. azorica were, in addition, the lowest reported among Macaronesian bird‐dispersed taxa. Lastly, low genetic differentiation was observed between subspecies occurring on the same island (sspp. platyphylla and lopezlilloi). In summary, our results revealed contrasting patterns between Macaronesian Ilex lineages: I. canariensis displayed moderate population structure across islands, whereas the I. perado complex showed strong differentiation among populations sampled on different islands. Thus, the Macaronesian Ilex taxa show that long‐distance dispersal syndromes (ornithochory) do not always ensure genetic connectivity across large areas in island systems. Plant groups that successfully colonized the islands on multiple occasions may have found barriers to gene flow within certain lineages. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 173 , 258–268. 相似文献
22.
Charlotte Gineste Yann Le Fur Christophe Vilmen Arnaud Le Troter Emilie Pecchi Patrick J. Cozzone Edna C. Hardeman David Bendahan Julien Gondin 《PloS one》2013,8(4)
Nemaline myopathy (NM) is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1) account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI) studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y). Skeletal muscle anatomy (hindlimb muscles and fat volumes) and energy metabolism were studied using MRI and 31Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1–150 Hz) and a fatigue protocol (80 stimuli at 40 Hz). H40Y mice showed a reduction of both absolute (−40%) and specific (−25%) maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40%) and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level. 相似文献
23.
Diana J. Kim Vignan Yogendrakumar Joyce Chiang Edna Ty Z. Jane Wang Martin J. McKeown 《PloS one》2013,8(7)
Noisy galvanic vestibular stimulation has been associated with numerous cognitive and behavioural effects, such as enhancement of visual memory in healthy individuals, improvement of visual deficits in stroke patients, as well as possibly improvement of motor function in Parkinson’s disease; yet, the mechanism of action is unclear. Since Parkinson’s and other neuropsychiatric diseases are characterized by maladaptive dynamics of brain rhythms, we investigated whether noisy galvanic vestibular stimulation was associated with measurable changes in EEG oscillatory rhythms within theta (4–7.5 Hz), low alpha (8–10 Hz), high alpha (10.5–12 Hz), beta (13–30 Hz) and gamma (31–50 Hz) bands. We recorded the EEG while simultaneously delivering noisy bilateral, bipolar stimulation at varying intensities of imperceptible currents – at 10, 26, 42, 58, 74 and 90% of sensory threshold – to ten neurologically healthy subjects. Using standard spectral analysis, we investigated the transient aftereffects of noisy stimulation on rhythms. Subsequently, using robust artifact rejection techniques and the Least Absolute Shrinkage Selection Operator regression and cross-validation, we assessed the combinations of channels and power spectral features within each EEG frequency band that were linearly related with stimulus intensity. We show that noisy galvanic vestibular stimulation predominantly leads to a mild suppression of gamma power in lateral regions immediately after stimulation, followed by delayed increase in beta and gamma power in frontal regions approximately 20–25 s after stimulation ceased. Ongoing changes in the power of each oscillatory band throughout frontal, central/parietal, occipital and bilateral electrodes predicted the intensity of galvanic vestibular stimulation in a stimulus-dependent manner, demonstrating linear effects of stimulation on brain rhythms. We propose that modulation of neural oscillations is a potential mechanism for the previously-described cognitive and motor effects of vestibular stimulation, and noisy galvanic vestibular stimulation may provide an additional non-invasive means for neuromodulation of functional brain networks. 相似文献
24.
Jared M. Baeten Renee Heffron Lara Kidoguchi Nelly R. Mugo Elly Katabira Elizabeth A. Bukusi Stephen Asiimwe Jessica E. Haberer Jennifer Morton Kenneth Ngure Nulu Bulya Josephine Odoyo Edna Tindimwebwa Craig Hendrix Mark A. Marzinke Norma C. Ware Monique A. Wyatt Susan Morrison Harald Haugen Andrew Mujugira Deborah Donnell Connie Celum Partners Demonstration Project Team 《PLoS medicine》2016,13(8)
BackgroundAntiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.ConclusionsIntegrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year. 相似文献
25.
Ana Paula Kallaur Josiane Lopes Sayonara Rangel Oliveira Andrea Name Colado Simão Edna Maria Vissoci Reiche Elaine Regina Delicato de Almeida Helena Kaminami Morimoto Wildea Lice Carvalho Jennings de Pereira Daniele Frizon Alfieri Sueli Donizete Borelli Domacio Ramon Kaimen-Maciel Michael Maes 《Molecular neurobiology》2016,53(8):5191-5202
26.
27.
Yada-Langui MM Anjos-Valotta EA Sannomiya P Rocha e Silva M Coimbra R 《Experimental biology and medicine (Maywood, N.J.)》2004,229(7):684-693
We have previously shown that lung injury following fluid resuscitation either with hypertonic saline (HS) or lactated Ringer's (LR) plus pentoxifylline (PTX) attenuated acute lung injury when compared with LR resuscitation. The objective of the present study is to determine whether our previous observations are accompanied by changes in polymorphonu-clear leukocyte (PMN) behavior. To study this, PMN-endothelial cell interactions, microcirculatory blood flow, lung histology, lung PMN infiltration (MPO, Myeloperoxidase), and lung intra-cellular adhesion molecule-1 (ICAM-1) expression were assessed in a controlled hemorrhagic shock model followed by LR, HS, and LR+PTX resuscitation in rodents. Rats (240-300 g) were bled to a mean arterial pressure (MAP) of 35 mm Hg for 1 hr and then randomized into three groups: HS (7.5% NaCl, 4 ml/kg); LR (3x shed blood); and LR+PTX (25 mg/kg). Additionally, total shed blood was reinfused. A sham group underwent no shock and no treatment. The internal spermatic fascia was exteriorized and the microcirculation was observed by closed-circuit TV coupled to a microscope, 2 and 6 hrs after treatment. The number of leukocytes sticking to the venular endothelium was determined 2 hrs after fluid resuscitation. Microcirculatory blood flow was measured by an optical Doppler velocimeter. Lung histology and lung MPO immunostaining were assessed at 6 hrs, and lung ICAM-1 expression was determined by immunostaining at 2 hrs following fluid resuscitation. Two hours after treatment, HS (1.4 +/- 0.4), LR+PTX (1.7 +/- 0.3), and sham (0.4 +/- 0.2) groups presented significant reductions in leukocyte adherence (cells/100 microm venule length), compared with the LR group (4.0 +/- 0.9, P < 0.05). No differences were observed 6 hrs after treatment on leukocyte adherence and microcirculatory blood flow. ICAM-1 expression was significantly higher in LR-treated animals compared with the HS, LR+PTX, and sham groups (P < 0.01). PMN infiltration and overall lung injury were significantly attenuated by HS and LR+PTX. These results support earlier studies that indicated the potential application of HS and PTX in shock therapy and the increase in PMN-endothelial cell interaction and lung injury after LR resuscitation. 相似文献
28.
Several drugs that interact with membrane sterols or inhibit their syntheses are effective in clearing a number of fungal infections. The AIDS-associated lung infection caused by Pneumocystis jirovecii is not cleared by many of these therapies. Pneumocystis normally synthesizes distinct C28 and C29 24-alkylsterols, but ergosterol, the major fungal sterol, is not among them. Two distinct sterol compositional phenotypes were previously observed in P. jirovecii. One was characterized by delta7 C28 and C29 24-alkylsterols with only low proportions of higher molecular mass components. In contrast, the other type was dominated by high C31 and C32 24-alkylsterols, especially pneumocysterol. In the present study, 28 molecular species were elucidated by nuclear magnetic resonance analysis of a human lung specimen containing P. jirovecii representing the latter sterol profile phenotype. Fifteen of the 28 had the methyl group at C-14 of the sterol nucleus and these represented 96% of the total sterol mass in the specimen (excluding cholesterol). These results strongly suggest that sterol 14alpha-demethylase was blocked in these organisms. Twenty-four of the 28 were 24-alkylsterols, indicating that methylation of the C-24 position of the sterol side chain by S-adenosyl-L-methionine:sterol C-24 methyl transferase was fully functional. 相似文献
29.
Catanozi S Rocha JC Passarelli M Guzzo ML Alves C Furukawa LN Nunes VS Nakandakare ER Heimann JC Quintão EC 《Journal of lipid research》2003,44(4):727-732
This study aimed at measuring the influence of a low salt diet on the development of experimental atherosclerosis in moderately hyperlipidemic mice. Experiments were carried out on LDL receptor (LDLR) knockout (KO) mice, or apolipoprotein E (apoE) KO mice on a low sodium chloride diet (LSD) as compared with a normal salt diet (NSD). On LSD, the rise of the plasma concentrations of TG and nonesterified fatty acid (NEFA) was, respectively, 19% and 34% in LDLR KO mice, and 21% and 35% in apoE KO mice, and that of plasma cholesterol was limited to the LDLR KO group alone (15%). Probably due to the apoE KO severe hypercholesterolemia, the arterial inner-wall fat storage was not influenced by the diet salt content and was far more abundant in the apoE KO than in the LDLR KO mice. However, in the less severe hypercholesterolemia of the LDLR KO mice, lipid deposits on the LSD were greater than on the NSD. Arterial fat storage correlated with NEFA concentrations in the LDLR KO mice alone (n = 14, P = 0.0065). Thus, dietary sodium chloride restriction enhances aortic wall lipid storage in moderately hyperlipidemic mice. 相似文献
30.