全文获取类型
收费全文 | 437篇 |
免费 | 46篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 14篇 |
2020年 | 6篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 9篇 |
2016年 | 16篇 |
2015年 | 25篇 |
2014年 | 19篇 |
2013年 | 22篇 |
2012年 | 26篇 |
2011年 | 31篇 |
2010年 | 20篇 |
2009年 | 13篇 |
2008年 | 21篇 |
2007年 | 24篇 |
2006年 | 26篇 |
2005年 | 20篇 |
2004年 | 14篇 |
2003年 | 21篇 |
2002年 | 13篇 |
2001年 | 13篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
排序方式: 共有483条查询结果,搜索用时 46 毫秒
51.
Sugey López-Martínez A. Berenice Aguilar-Guadarrama María Yolanda Rios 《Phytochemistry letters》2011,4(3):275-279
From the fresh roots of Heliopsis longipes three new minor alkamides: longipinamide A (N-isobutyl-8,10-diynoic-3Z-undecenamide), longipenamide A (N-isobutyl-syn-8,9-dihydroxy-2E,6Z-decadienamide) and longipenamide B (N-isobutyl-syn-6,9-dihydroxy-2E,7E-decadienamide); three known alkamides: affinin (spilanthol, N-isobutyl-2E,6Z,8E-decatrienamide), N-isobutyl-2E,6Z-decadienamide and N-isobutyl-2E-decenamide; and 11 other known compounds were isolated. The structures of the three new minor alkamides were established by 1D and 2D NMR spectroscopy including 1H, 13C, DEPT, COSY, HSQC, and HMBC experiments, as well as by EI and FAB+ mass spectrometry. To our knowledge, this is the first report of the isolation of linear dihydroxyalkamides as natural products. 相似文献
52.
Peter JD Andrews Helen Louise Sinclair Claire G Battison Kees H Polderman Giuseppe Citerio Luciana Mascia Bridget A Harris Gordon D Murray Nino Stocchetti David K Menon Haleema Shakur Daniel De Backer 《Trials》2011,12(1):1-13
Background
Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2) has recently been shown to function as a key regulator. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO) gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates.Methods/Design
This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy), among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae.Discussion
Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa.Trial Registration
ClinicalTrials.gov Identifier: NCT01255215 相似文献53.
Leovigildo Quijano Jose S. Calderon G.Federico Gomez P.Jesus Lopez Tirso Rios Frank R. Fronczek 《Phytochemistry》1984,23(9):1971-1974
A chloroform extract of Montanoa grandiflora afforded a novel 6β-hydroxy-germacradien-8,12-olide. Its structure was shown to be 6-epi-desacetyllaurenobiolide by spectral studies, chemical transformations and single crystal X-ray diffraction. The X-ray data demonstrate that the ten-membered ring exists in the crystal in the highly unusual [15D5,1D14] conformation, in which the methyl group at C-4 is α-oriented and the methyl group at C-10 is β-oriented. The two double bonds are approximately parallel rather than crossed. 相似文献
54.
Piazza F Rios Pde L Fanelli D Bongini L Skoglund U 《European biophysics journal : EBJ》2005,34(7):899-911
The encounter between anisotropic agents in diffusion-controlled reactions is a topic of very general relevance in chemistry and biology. Here we introduce a simplified model of encounter of an isotropic molecule with a pair of partially reacting agents and apply it to the encounter reaction between an antibody and its antigen. We reduce the problem to the solution of dual series relations, which can be solved iteratively, yielding the exact solution for the encounter rate constant at any desired order of accuracy. We quantify the encounter effectiveness by means of a simple indicator and show that the two binding centers systematically behave in an anti-cooperative fashion. However, we demonstrate that a reduction of the binding active sites allows the composite molecule to recover binding effectiveness, in spite of the overall reduction of the rate constant. In addition, we provide a simple formula that enables one to calculate the anti-cooperativity as a function of the size of the binding site for any values of the separation between the two active lobes and of the antigen size. Finally, some biological implications of our results are discussed. 相似文献
55.
Gadelha SR Alcantara LC Costa GC Rios DL Galvão-Castro B 《Human biology; an international record of research》2005,77(4):509-514
Polymorphisms in the interleukin-6 promoter region have been associated with diseases. In this study we investigated the -634G/C and -174G/C IL-6 promoter polymorphisms in three Brazilian ethnic groups. We verified that the allele frequencies of the two polymorphisms and haplotype frequencies varied significantly between the populations. 相似文献
56.
The bidentate complex of ATP with Cr(3+), CrATP, is a nucleotide analog that is known to inhibit the sarcoplasmic reticulum Ca(2+)-ATPase and the Na(+),K(+)-ATPase, so that these enzymes accumulate in a conformation with the transported ion (Ca(2+) and Na(+), respectively) occluded from the medium. Here, it is shown that CrATP is also an effective and irreversible inhibitor of the plasma membrane Ca(2+)-ATPase. The complex inhibited with similar efficiency the Ca(2+)-dependent ATPase and the phosphatase activities as well as the enzyme phosphorylation by ATP. The inhibition proceeded slowly (T(1/2)=30 min at 37 degrees C) with a K(i)=28+/-9 microM. The inclusion of ATP, ADP or AMPPNP in the inhibition medium effectively protected the enzyme against the inhibition, whereas ITP, which is not a PMCA substrate, did not. The rate of inhibition was strongly dependent on the presence of Mg(2+) but unaltered when Ca(2+) was replaced by EGTA. In spite of the similarities with the inhibition of other P-ATPases, no apparent Ca(2+) occlusion was detected concurrent with the inhibition by CrATP. In contrast, inhibition by the complex of La(3+) with ATP, LaATP, induced the accumulation of phosphoenzyme with a simultaneous occlusion of Ca(2+) at a ratio close to 1.5 mol/mol of phosphoenzyme. The results suggest that the transport of Ca(2+) promoted by the plasma membrane Ca(2+)-ATPase goes through an enzymatic phospho-intermediate that maintains Ca(2+) ions occluded from the media. This intermediate is stabilized by LaATP but not by CrATP. 相似文献
57.
Gianotti A Rios WM Soares-Costa A Nogaroto V Carmona AK Oliva ML Andrade SS Henrique-Silva F 《Protein expression and purification》2006,47(2):483-489
Phytocystatins are cysteine proteinase inhibitors from plants implicated in the endogenous regulation of protein turnover, programmed cell death, and in defense mechanisms against pathogens. To date, only few cystatin genes have been characterized in most plant species. We have previously characterized the protein Canecystatin, the first cystatin described in sugarcane. In an attempt to study novel Canecystatins, we identified two ORFs encoding cystatins (referred as CaneCPI-2 and CaneCPI-3) using the data from the Sugarcane EST genome project. These ORFs were then subcloned and expressed in Escherichia coli using pET28 expression vector. High amounts (approximately 20 mg/L) of pure recombinant proteins were obtained by affinity chromatography in a single step of purification. Polyclonal antibodies against the recombinant Canecystatins were raised, allowing the immunodetection of the endogenous proteins in the plant tissues. Moreover, the proteins were able to inhibit papain in a fluorometric assay with K(i) values of 0.2 and 0.25 microM for CaneCPI-2 and CaneCPI-3, respectively. These findings contribute to a better understanding of the activity of sugarcane cystatins and encourage future activity and structural studies of these proteins. 相似文献
58.
Talita C. Morais Natália B. Pinto Karine Maria M.B. Carvalho Jeison B. Rios Nagila Maria P.S. Ricardo Maria Teresa S. Trevisan Vietla S. Rao Flávia A. Santos 《Chemico-biological interactions》2010,183(1):264-269
Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2 mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100 mg/kg), misoprostol (50 μg/kg), or vehicle (2% Tween 80 in saline, 10 mL/kg), 45 min before ethanol administration. They were sacrificed 30 min later, the stomachs excised, and the mucosal lesion area (mm2) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K+ATP channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation. 相似文献
59.
An open-access long oligonucleotide microarray resource for analysis of the human and mouse transcriptomes
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
60.
We examined the influence of riparian vegetation on macroinvertebrate community structure in streams of the Upper Thames River
watershed in southwestern Ontario. Thirty-three μ-basins (129–1458 ha) were used to identify land cover variables that influenced
stream macroinvertebrates. Micro-basins represented the entire drainage area of study streams and were similar in stream order
(first, second) and land cover (agricultural or forest; no urban). We described the structure and composition of riparian
vegetation and benthic macroinvertebrate communities at the outflow reach. The nature of the land cover was quantified for
the stream network buffer (30 m) and the whole μ-basin. The objective of this study was to measure the magnitude and nature
of the relationship between the riparian vegetation and benthic macroinvertebrate community at the outflow reach, stream network
buffer, and whole μ-basin scales. Taxon richness (including total number of Ephemeroptera, Plecoptera, and Trichoptera taxa)
and Simpson’s diversity of the macroinvertebrate community all increased with increased tree cover in the riparian zone at
the outflow reach scale. Simpson’s equitability was lower with greater agricultural land cover in the stream network buffer.
No relationship between the macroinvertebrate community and land cover was found at the whole μ-basin scale. Analysis of the
influence of land cover on stream communities within a spatial hierarchy is important for understanding the interactions of
stream ecosystems with their adjacent landscapes. 相似文献