全文获取类型
收费全文 | 1130篇 |
免费 | 103篇 |
出版年
2021年 | 17篇 |
2020年 | 8篇 |
2019年 | 17篇 |
2018年 | 23篇 |
2017年 | 17篇 |
2016年 | 27篇 |
2015年 | 46篇 |
2014年 | 39篇 |
2013年 | 53篇 |
2012年 | 70篇 |
2011年 | 88篇 |
2010年 | 56篇 |
2009年 | 46篇 |
2008年 | 52篇 |
2007年 | 77篇 |
2006年 | 58篇 |
2005年 | 74篇 |
2004年 | 59篇 |
2003年 | 55篇 |
2002年 | 52篇 |
2001年 | 16篇 |
2000年 | 9篇 |
1999年 | 14篇 |
1998年 | 17篇 |
1997年 | 21篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 12篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1977年 | 8篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1971年 | 7篇 |
1969年 | 6篇 |
1968年 | 5篇 |
1965年 | 4篇 |
1960年 | 4篇 |
排序方式: 共有1233条查询结果,搜索用时 15 毫秒
991.
The presence of 1.0 M KCl or NaCl during growth of Debaryomyces hansenii results in increased ethanol production. An additional increase of fermentation was observed when the salts were also present during incubation under nongrowing conditions. Extracts of cells grown in the presence of salt showed increased alcohol dehydrogenase and phosphofructokinase activities, indicating that these enzymes are responsible for the increased fermentation capacity. This is confirmed by measurements of the glycolytic intermediates. The increased fermentation capacity of the cells grown with salts seems to enable them to cope with the additional energy required for uptake and/or efflux of cations. 相似文献
992.
During a parasitological survey of Galaxias maculatus (Jenyns) from Patagonian Andean Lakes, specimens of a new species of nematode were collected from the stomach of fish and studied by light and scanning electron microscopy. This species is described as the only member of a newly proposed genus of Cystidicolidae by having oral opening dorsoventrally elongated, 2 lateral pseudolabia, 4 cephalic papillae, stoma (vestibule) elongated, esophagus divided into anterior muscular and posterior glandular sections, and caudal alae in males. Placonema n. gen. (Habronematoidea, Cystidicolidae) is characterized by the combination of the following features: oral opening dorsoventrally elongated demarcated by 4 sclerotized plates and 2 well-developed pseudolabia projected to the buccal cavity, each pseudolabium with conspicuous, conical, anterior protuberances. Four cephalic papillae and deirids simple. Male with caudal alae, area rugosa absent, 4 pairs of preanal papillae, unpaired papilla present on anterior cloacal lip, and 6 pairs of postanal papillae. Larvigerous eggs without filaments. Placonema pataguense n. gen. n. sp. infects the stomach of G. maculatus from Lake Patagua (Patagonia, Argentina) and is the first species of Cystidicolidae described from G. maculatus. 相似文献
993.
David J. Bacon Doug Tang Carola Salas Norma Roncal Carmen Lucas Lucia Gerena Lorena Tapia A. Alejandro Llanos-Cuentas Coralith Garcia Lelv Solari Dennis Kyle Alan J. Magill 《PloS one》2009,4(8)
Background
Sulfadoxine-pyrimethamine was a common first line drug therapy to treat uncomplicated falciparum malaria, but increasing therapeutic failures associated with the development of significant levels of resistance worldwide has prompted change to alternative treatment regimes in many national malaria control programs.Methodology and Finding
We conducted an in vivo therapeutic efficacy trial of sulfadoxine-pyrimethamine at two locations in the Peruvian Amazon enrolling 99 patients of which, 86 patients completed the protocol specified 28 day follow up. Our objective was to correlate the presence of polymorphisms in P. falciparum dihydrofolate reductase and dihydropteroate synthase to in vitro parasite susceptibility to sulfadoxine and pyrimethamine and to in vivo treatment outcomes. Inhibitory concentration 50 values of isolates increased with numbers of mutations (single [108N], sextuplet [BR/51I/108N/164L and 437G/581G]) and septuplet (BR/51I/108N/164L and 437G/540E/581G) with geometric means of 76 nM (35–166 nM), 582 nM (49-6890- nM) and 4909 (3575–6741 nM) nM for sulfadoxine and 33 nM (22–51 nM), 81 nM (19–345 nM), and 215 nM (176–262 nM) for pyrimethamine. A single mutation present in the isolate obtained at the time of enrollment from either dihydrofolate reductase (164L) or dihydropteroate synthase (540E) predicted treatment failure as well as any other single gene alone or in combination. Patients with the dihydrofolate reductase 164L mutation were 3.6 times as likely to be treatment failures [failures 85.4% (164L) vs 23.7% (I164); relative risk = 3.61; 95% CI: 2.14 – 6.64] while patients with the dihydropteroate synthase 540E were 2.6 times as likely to fail treatment (96.7% (540E) vs 37.5% (K540); relative risk = 2.58; 95% CI: 1.88 – 3.73). Patients with both dihydrofolate reductase 164L and dihydropteroate synthase 540E mutations were 4.1 times as likely to be treatment failures [96.7% vs 23.7%; RR = 4.08; 95% CI: 2.45 – 7.46] compared to patients having both wild forms (I164 and K540).Conclusions
In this part of the Amazon basin, it may be possible to predict treatment failure with sulfadoxine-pyrimethamine equally well by determination of either of the single mutations dihydrofolate reductase 164L or dihydropteroate synthase 540E.Trial Registration
ClinicalTrials.gov NCT00951106 NCT00951106相似文献994.
995.
Sandra E. Zulian Mónica G. Ilincheta de Boschero Norma M. Giusto 《Neurochemical research》2009,34(7):1236-1248
The highly efficient formation of phosphatidic acid from exogenous 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) in rat brain synaptic nerve endings (synaptosomes) from cerebral cortex and hippocampus is reported. Phosphatidic
acid synthesized from SAG or 1,2-dipalmitoyl-sn-glycerol (DPG) was 17.5 or 2.5 times higher, respectively, than from endogenous synaptosomal diacylglycerides. Insulin increased
diacylglycerol kinase (DAGK) action on endogenous substrate in synaptic terminals from hippocampus and cerebral cortex by
199 and 97%, respectively. Insulin preferentially increased SAG phosphorylation from hippocampal membranes. In CC synaptosomes
insulin increased phosphatidic acid (PA) synthesis from SAG by 100% with respect to controls. Genistein (a tyrosine kinase
inhibitor) inhibited this stimulatory insulin effect. Okadaic acid or cyclosporine, used as Ser/Threo protein phosphatase
inhibitors, failed to increase insulin effect on PA formation. GTPγS and particularly NaF were potent stimulators of PA formation
from polyunsaturated diacylglycerol but failed to increase this phosphorylation when added after 5 min of insulin exposure.
GTPγS and NaF increased phosphatidylinositol 4,5 bisphosphate (PIP2) labeling with respect to controls when SAG was present.
On the contrary, they decreased polyphosphoinositide labeling with respect to controls in the presence of DPG. Our results
indicate that a DAGK type 3 (DAGKε) which preferentially, but not selectively, utilizes 1-acyl-2-arachidonoyl-sn-glycerol and which could be associated with polyphosphoinositide resynthesis, participates in synaptic insulin signaling.
GTPγS and NaF appear to be G protein activators related to insulin and the insulin receptor, both affecting the signaling
mechanism that augments phosphatidic acid formation. 相似文献
996.
Castro-Guerrero N Sinha PK Torres-Bacete J Matsuno-Yagi A Yagi T 《Biochemistry》2010,49(47):10072-10080
The prokaryotic proton-translocating NADH-quinone oxidoreductase (NDH-1) is an L-shaped membrane-bound enzyme that contains 14 subunits (NuoA-NuoN or Nqo1-Nqo14). All subunits have their counterparts in the eukaryotic enzyme (complex I). NDH-1 consists of two domains: the peripheral arm (NuoB, -C, -D, -E, -F, -G, and -I) and the membrane arm (NuoA, -H, -J, -K, -L, -M, and -N). In Escherichia coli NDH-1, the hydrophilic subunits NuoC/Nqo5/30k and NuoD/Nqo4/49k are fused together in a single polypeptide as the NuoCD subunit. The NuoCD subunit is the only subunit that does not bear a cofactor in the peripheral arm. While some roles for inhibitor and quinone association have been reported for the NuoD segment, structural and functional roles of the NuoC segment remain mostly elusive. In this work, 14 highly conserved residues of the NuoC segment were mutated and 21 mutants were constructed using the chromosomal gene manipulation technique. From the enzymatic assays and immunochemical and blue-native gel analyses, it was found that residues Glu-138, Glu-140, and Asp-143 that are thought to be in the third α-helix are absolutely required for the energy-transducing NDH-1 activities and the assembly of the whole enzyme. Together with available information for the hydrophobic subunits, we propose that Glu-138, Glu-140, and Asp-143 of the NuoC segment may have a pivotal role in the structural stability of NDH-1. 相似文献
997.
The epidemiology of cryptosporidiosis, an infection caused by several genotypically and phenotypically diverse Cryptosporidium species, has been dynamically changing over the past decade from that of a rare, largely asymptomatic infection to an acute enteric disease of animals and humans. In this review, the current understanding of factors (biology and epidemiology) contributing to the emergence of cryptosporidiosis in animals, including parasite biology, genetic diversity, environmental spread, livestock production trends, presence of the parasite in livestock and companion animals, and potential risk of transmission from animals to humans is highlighted. Potential control measures and the role of veterinary and medical professionals in the prevention of cryptosporidiosis are also discussed. 相似文献
998.
999.
A new species of Catatropis Oghner, 1905 from a freshwater Neotropical prosobranch snail, Heleobia hatcheri (Hydrobiidae), is described. Naturally infected snails were collected from Nahuel Huapí Lake in Andean Patagonia. The characteristics of the larval stages are also presented. Experimental adults were recovered from the distal region of the intestinal caeca of chicks and ducklings and natural adults from a wild duck Anas platyrhynchos. Adults of Catatropis hatcheri n. sp. can be distinguished from all other species of the genus in having 10-12 (11) ventral glands in each lateral row, the cirrus-sac extending back to between the first third and the middle of the body, the metraterm shorter than the cirrus-sac, a previtelline field of 1,258-1,544 (1,396), vitelline follicles reach back to the anterior border of the testes with some follicles extending slightly lateral to them, only external testicular margin lobed and genital pore in median line just posterior to the intestinal bifurcation. In addition, the eggs have one filament on each pole, the rediae contain one or two mature cercariae, and the cercariae are tri-oculate, with a long tail and encyst in the environment. 相似文献
1000.
Cao W Cheng L Behar J Biancani P Harnett KM 《American journal of physiology. Gastrointestinal and liver physiology》2006,291(4):G672-G680
In a cat model of acute experimental esophagitis, resting in vivo lower esophageal sphincter (LES) pressure and in vitro tone are lower than in normal LES, and the LES circular smooth muscle layer contains elevated levels of IL-1beta that decrease the LES tone of normal cats. We now examined the mechanisms of IL-1beta-induced reduction in LES tone. IL-1beta significantly reduced acetylcholine-induced Ca(2+) release in Ca(2+)-free medium, and this effect was partially reversed by catalase, demonstrating a role of H(2)O(2) in these changes. IL-1beta significantly increased the production of H(2)O(2), and the increase was blocked by the p38 MAPK inhibitor SB-203580, by the cytosolic phospholipase A(2) (cPLA(2)) inhibitor AACOCF3, and by the NADPH oxidase inhibitor apocynin, but not by the MEK1 inhibitor PD-98059. IL-1beta significantly increased the phosphorylation of p38 MAPK and cPLA(2). IL-1beta-induced cPLA(2) phosphorylation was blocked by SB-203580 but not by AACOCF3, suggesting sequential activation of p38 MAPK-phosphorylating cPLA(2). The IL-1beta-induced reduction in LES tone was partially reversed by AACOCF3 and by the Ca(2+)-insensitive PLA(2) inhibitor bromoenol lactone (BEL). IL-1beta significantly increased cyclooxygenase (COX)-2 and PGE(2) levels. The increase in PGE(2) was blocked by SB-203580, AACOCF3, BEL, and the COX-2 inhibitor NS-398 but not by PD-98059 or the COX-1 inhibitor valeryl salicylate. The data suggested that IL-1beta reduces LES tone by producing H(2)O(2), which may affect Ca(2+)-release mechanisms and increase the synthesis of COX-2 and PGE(2). Both H(2)O(2) and PGE(2) production depend on sequential activation of p38 MAPK and cPLA(2). cPLA(2) activates NADPH oxidases, producing H(2)O(2), and may produce arachidonic acid, converted to PGE(2) via COX-2. 相似文献