全文获取类型
收费全文 | 760篇 |
免费 | 49篇 |
国内免费 | 2篇 |
出版年
2023年 | 3篇 |
2022年 | 14篇 |
2021年 | 18篇 |
2020年 | 9篇 |
2019年 | 11篇 |
2018年 | 16篇 |
2017年 | 21篇 |
2016年 | 18篇 |
2015年 | 34篇 |
2014年 | 30篇 |
2013年 | 66篇 |
2012年 | 62篇 |
2011年 | 71篇 |
2010年 | 38篇 |
2009年 | 39篇 |
2008年 | 38篇 |
2007年 | 36篇 |
2006年 | 27篇 |
2005年 | 42篇 |
2004年 | 34篇 |
2003年 | 34篇 |
2002年 | 17篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1933年 | 1篇 |
排序方式: 共有811条查询结果,搜索用时 15 毫秒
41.
42.
Antti T. Muuronen Mikko Taina Marja Hedman Jarkko Marttila Johanna Kuusisto Juha Onatsu Ritva Vanninen Pekka J?k?l? Petri Sipola Pirjo Mustonen 《PloS one》2015,10(3)
Purpose
The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.Methods
Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered.Results
Mean VAT area was significantly higher in stroke patients (205±103 cm2 for men and 168±99 cm2 for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors.Conclusion
Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients. 相似文献43.
Saara Laulumaa Tuomo Nieminen Mari Lehtim?ki Shweta Aggarwal Mikael Simons Michael M. Koza Ilpo Vattulainen Petri Kursula Francesca Natali 《PloS one》2015,10(6)
Myelin protein P2 is a fatty acid-binding structural component of the myelin sheath in the peripheral nervous system, and its function is related to its membrane binding capacity. Here, the link between P2 protein dynamics and structure and function was studied using elastic incoherent neutron scattering (EINS). The P38G mutation, at the hinge between the β barrel and the α-helical lid, increased the lipid stacking capacity of human P2 in vitro, and the mutated protein was also functional in cultured cells. The P38G mutation did not change the overall structure of the protein. For a deeper insight into P2 structure-function relationships, information on protein dynamics in the 10 ps to 1 ns time scale was obtained using EINS. Values of mean square displacements mainly from protein H atoms were extracted for wild-type P2 and the P38G mutant and compared. Our results show that at physiological temperatures, the P38G mutant is more dynamic than the wild-type P2 protein, especially on a slow 1-ns time scale. Molecular dynamics simulations confirmed the enhanced dynamics of the mutant variant, especially within the portal region in the presence of bound fatty acid. The increased softness of the hinge mutant of human myelin P2 protein is likely related to an enhanced flexibility of the portal region of this fatty acid-binding protein, as well as to its interactions with the lipid bilayer surface requiring conformational adaptations. 相似文献
44.
Petri Kemppainen Christopher G. Knight Devojit K. Sarma Thaung Hlaing Anil Prakash Yan Naung Maung Maung Pradya Somboon Jagadish Mahanta Catherine Walton 《Molecular ecology resources》2015,15(5):1031-1045
Recent advances in sequencing allow population‐genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction‐site‐associated DNA sequence (RAD‐seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well‐characterized single nucleotide polymorphism (SNP) data set from 21 three‐spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single‐outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population‐genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population‐demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population‐genomic data set, making it especially valuable for nonmodel species. 相似文献
45.
46.
Otso Arponen Antti Muuronen Mikko Taina Petri Sipola Marja Hedman Pekka J?k?l? Ritva Vanninen Kari Pulkki Pirjo Mustonen 《PloS one》2015,10(4)
Background
Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.Methods
A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.Results
Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.Conclusion
IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology. 相似文献47.
Eero Lauhkonen Petri Koponen Johanna Ter?sj?rvi Kirsi Gr?ndahl-Yli-Hannuksela Juho Vuononvirta Kirsi Nuolivirta Jyri O. Toikka Merja Helminen Qiushui He Matti Korppi 《PloS one》2015,10(10)
Aim
Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age.Methods
We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children.Results
IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise.Conclusion
Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients. 相似文献48.
D. Ragancokova Y. Song H. Nau R. Dengler K. Krampfl S. Petri 《Cellular and molecular neurobiology》2010,30(6):891-900
Amyotrophic lateral sclerosis is a devastating motoneuron disorder for which no effective treatment exists. There is some
evidence for neuroprotective effects of valproic acid (VPA). The beneficial effects, however, are limited due to the adverse
effects of VPA. To overcome this problem, a number of VPA derivates with fewer side effects have been synthesized. In the
present study, we investigated the viability of highly purified embryonic motoneurons cultured on glial feeder layers, composed
of either astrocytes or Schwann cells, or in monoculture, in presence of VPA and its three derivates 3-propyl-heptanoic acid
(3-PHA), PE-4-yn enantiomers (R- and S-PE-4-yn). An excitotoxic stimulus, kainate (KA), was added at day in vitro 9 (DIV9)
and the neuroprotective effect of either simultaneous incubation (DIV9) or pre-incubation (DIV1) of VPA and its derivates
was tested. The survival of motoneurons under simultaneous application of KA and VPA derivates was not remarkably increased.
Pre-incubation with VPA and even more with the derivates before the addition of KA, however, significantly reduced their vulnerability
against the KA-induced neurotoxic effect. Our data suggest that the neuroprotective capacities of VPA and its three derivates
tested here drastically increase when they are added several days before KA. Most prominent neuroprotective effects were seen
for the PE-4-yn enantiomers. Patch-clamp experiments revealed an antiexcitotoxic effect of the S-PE-4-yn enantiomer that reduces
the frequency of postsynaptic currents and enhances the inhibitory postsynaptic transmission dependent on the co-culture condition. 相似文献
49.
Viivi Majava Chaozhan Wang Matti Myllykoski Salla M. Kangas Sung Ung Kang Nobuhiro Hayashi Peter Baumgärtel Anthony M. Heape Gert Lubec Petri Kursula 《Amino acids》2010,39(1):59-71
Myelin basic protein (MBP) is present between the cytoplasmic leaflets of the compact myelin membrane in both the peripheral and central nervous systems, and characterized to be intrinsically disordered in solution. One of the best-characterized protein ligands for MBP is calmodulin (CaM), a highly acidic calcium sensor. We pulled down MBP from human brain white matter as the major calcium-dependent CaM-binding protein. We then used full-length brain MBP, and a peptide from rodent MBP, to structurally characterize the MBP–CaM complex in solution by small-angle X-ray scattering, NMR spectroscopy, synchrotron radiation circular dichroism spectroscopy, and size exclusion chromatography. We determined 3D structures for the full-length protein–protein complex at different stoichiometries and detect ligand-induced folding of MBP. We also obtained thermodynamic data for the two CaM-binding sites of MBP, indicating that CaM does not collapse upon binding to MBP, and show that CaM and MBP colocalize in myelin sheaths. In addition, we analyzed the post-translational modifications of rat brain MBP, identifying a novel MBP modification, glucosylation. Our results provide a detailed picture of the MBP–CaM interaction, including a 3D model of the complex between full-length proteins. 相似文献
50.
Phospholipids are key components of biological membranes and their lipolysis with phospholipase A2 (PLA2) enzymes occurs in different cellular pH environments. Since no studies are available on the effect of pH on PLA2-modified phospholipid membranes, we performed 50-ns atomistic molecular dynamics simulations at three different pH conditions (pH 9.0, 7.5, and 5.5) using a fully PLA2-hydrolyzed phosphatidylcholine (PC) bilayer which consists solely of lysophosphatidylcholine and free fatty acid molecules. We found that a decrease in pH results in lateral squeezing of the membrane, i.e. in decreased surface area per headgroup. Thus, at the decreased pH, the lipid hydrocarbon chains had larger SCD order parameter values, and also enhanced membrane thickness, as seen in the electron density profiles across the membrane. From the lateral pressure profiles, we found that the values of spontaneous curvature of the two opposing monolayers became negative when the pH was decreased. At low pH, protonation of the free fatty acid headgroups reduces their mutual repulsion and accounts for the pH dependence of all the above-mentioned properties. The altered structural characteristics may significantly affect the overall surface properties of biomembranes in cellular vesicles, lipid droplets, and plasma lipoproteins, play an important role in membrane fission and fusion, and modify interactions between membrane lipids and the proteins embedded within them. 相似文献