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991.
Selecting your first postdoctoral position 总被引:1,自引:0,他引:1
Fuller CM 《The Physiologist》2008,51(1):20-21
992.
D D Fuller A G Zabka T L Baker G S Mitchell 《Journal of applied physiology》2001,90(5):2001-6; discussion 2000
Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (integralPhr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial PO(2) = 40 +/- 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [1) control (n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia (n = 7 each)]. Ketanserin transiently decreased integralPhr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, integralPhr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF. 相似文献
993.
Kex2 protease from Saccharomyces cerevisiae is the prototype for a family of eukaryotic proprotein processing proteases belonging to the subtilase superfamily of serine proteases. Kex2 can be distinguished from degradative subtilisins on the basis of stringent substrate specificity and distinct pre-steady-state behavior. To better understand these mechanistic differences, we have examined the effects of substrate residues at P(1) and P(4) on individual steps in the Kex2 catalytic cycle with a systematic series of isosteric peptidyl amide and ester substrates. The results demonstrate that substrates based on known, physiological cleavage sites exhibit high acylation rates (> or =550 s(-1)) with Kex2. Substitution of Lys for the physiologically correct Arg at P(1) resulted in a > or =200-fold drop in acylation rate with almost no apparent effect on binding or deacylation. In contrast, substitution of the physiologically incorrect Ala for Nle at P(4) resulted in a much smaller defect in acylation and a modest but significant effect on binding with Lys at P(1). This substitution also had no effect on deacylation. These results demonstrate that Kex2 utilizes enzyme-substrate interactions in different ways at different steps in the catalytic cycle, with the S(1)-P(1) contact providing a key specificity determinant at the acylation step. 相似文献
994.
Differential centrifugation separates cardiac sarcolemmal and endosomal membranes from Langendorff-perfused rat hearts 总被引:1,自引:0,他引:1
The application of subcellular fractionation protocols developed in soft tissues to fibrous organs such as the heart is unsuitable given the substantial differences in subcellular structure these tissues exhibit. The purpose of this study was to develop a simple method for the separation of sarcolemma and endosomes from isolated Langendorff-perfused rat hearts. Hearts were homogenized with either an Ultra-Turrax homogenizer or a hand-held glass tissue grinder. Quantitative immunoblots assessed the enrichment of the sarcolemmal proteins caveolin 3 and the sodium potassium ATPase and the endosomal proteins rab4 and GLUT4 in different membrane fractions. Application of homogenates to sucrose and Percoll density gradients failed to resolve membranes differentially enriched in sarcolemmal or endosomal marker proteins, indicating little difference in density between the sarcolemma and endosomes. However, successive spins of homogenates from a hand-held glass tissue grinder successfully separated the endosomes from the sarcolemma, indicating differences in masses between the two membrane fractions. Approximately 70% of total caveolin 3 and sodium potassium ATPase immunoreactivity was in membrane pellets up to 20,000g and approximately 85% of rab4 and GLUT4 in pellets from 20,000-100,000g. In addition, 86% of ouabain-sensitive ATPase activity (sodium potassium ATPase activity) was in membrane pellets up to 20,000g. Therefore, sarcolemmal membranes were pelleted up to 20,000g, and endosomal membranes between 20,000 and 100,000g. Regional ischemia (40 min) followed by reperfusion (60 min) caused the translocation of GLUT4 (but not rab4) from the endosomal membranes to the sarcolemma in the area of the heart subjected to ischemia. 相似文献
995.
Fuller MA Weichert H Fischer AM Feussner I Grimes HD 《Archives of biochemistry and biophysics》2001,388(1):146-154
In soybean (Glycine max L.) vegetative tissue at least five lipoxygenase isozymes are present. Four of these proteins have been localized to the paraveinal mesophyll, a layer of cells that is thought to function in assimilate partitioning. In order to determine the role of the lipoxygenase isozymes within the soybean plant, the leaf lipoxygenases were cloned into bacterial expression vectors and expressed in Escherichia coil. The recombinant lipoxygenases were then characterized as to substrate preference, pH profiles for the most common plant lipoxygenase substrates, linoleic acid, and alpha-linolenic acid, and the reaction products with the substrates linoleic acid, alpha-linolenic acid, arachidonic acid, gamma-linolenic acid, and the triacylglycerol trilinolein. All five enzymes were shown to be (13S)-lipoxygenases against linoleic acid. The results of these assays also indicate that two of these isozymes are highly active against esterified fatty acid groups, such as those found in triacylglycerols. Lipid analysis of leaves from plants subjected to sink limitation conditions indicates that the soybean leaf lipoxygenases are active in vivo against both free fatty acids and esterified lipids, and that the quantities of lipoxygenase products found in leaf tissue show a positive correlation with the level of lipoxygenase in the leaf. Implications for the putative role of these enzymes in the paraveinal mesophyll are discussed. 相似文献
996.
Male Zucker rats were exposed to 2 G for 8 wk to test the hypothesis that the leptin regulatory pathway contributes to recovery from effects of 2 G on feeding, growth, and nutrient partitioning. After initial hypophagia, body mass-independent food intake of the lean rats exposed to 2 G surpassed that of the lean rats maintained at 1 G, but food intake of the obese rats exposed to 2 G remained low. After 8 wk at 2 G, body mass and carcass fat were less in both genotypes. Leptin and percent fat were lower in lean rats exposed to 2 G vs. 1 G but did not differ in obese rats exposed to 2 G vs. 1 G. Although exposure to 2 G did not alter uncoupling protein-1 levels, it did elicit white fat pad-specific changes in lipoprotein lipase activity in obese but not lean rats. We conclude that 2 G affects both genotypes but that the lean Zucker rats recover their food intake and growth rate and retain "normal" lipoprotein lipase activity to a greater degree than do the obese rats, emphasizing the importance of a functional leptin regulatory pathway in this acclimation. 相似文献
997.
Ventilatory long-term facilitation in unanesthetized rats 总被引:5,自引:0,他引:5
Olson E. B. Jr.; Bohne C. J.; Dwinell M. R.; Podolsky A.; Vidruk E. H.; Fuller D. D.; Powell F. L.; Mitchel G. S. 《Journal of applied physiology》2001,91(2):709-716
Wetested the hypothesis that unanesthetized rats exhibit ventilatorylong-term facilitation (LTF) after intermittent, but not continuous,hypoxia. Minute ventilation (E) and carbon dioxide production (CO2) were measured inunanesthetized, unrestrained male Sprague-Dawley rats via barometricplethysmography before, during, and after exposure to continuous orintermittent hypoxia. Hypoxia was either isocapnic [inspiredO2 fraction (FIO2) = 0.08-0.09 and inspired CO2 fraction(FICO2) = 0.04] or poikilocapnic(FIO2 = 0.11 andFICO2 = 0.00). Sixty minutes afterintermittent hypoxia, E orE/CO2 wassignificantly greater than baseline in both isocapnic and poikilocapnicconditions. In contrast, 60 min after continuous hypoxia,E andE/CO2 were notsignificantly different from baseline values. These data demonstrateventilatory LTF after intermittent hypoxia in unanesthetized rats.Ventilatory LTF appeared similar in its magnitude (after accounting forCO2 feedback), time course, and dependence on intermittenthypoxia to phrenic LTF previously observed in anesthetized,vagotomized, paralyzed rats. 相似文献
998.
999.
Blood pressure response to standing in the diagnosis of autonomic neuropathy: the EURODIAB IDDM Complications Study 总被引:2,自引:0,他引:2
Kempler P Tesfaye S Chaturvedi N Stevens LK Webb DJ Eaton S Kerényi Z Tamás G Ward JD Fuller JH 《Archives of physiology and biochemistry》2001,109(3):215-222
Autonomic neuropathy is associated with poor prognosis. Cardiovascular reflexes are essential for the diagnosis of autonomic nerve dysfunction. Blood pressure response to standing is the most simple test for the evaluation of sympathetic integrity, however it is still discussed which diagnostic criteria of abnormal response should be considered as optimal. The EURODIAB IDDM Complications Study involved the examination of randomly selected Type 1 diabetic patients from 31 centres in 16 European counties. Data from 3007 patients were available for the present evaluation. Two tests of autonomic function (response of heart rate /R-R ratio/ and blood pressure from lying to standing) just as the frequency of feeling faint on standing up were assessed. R-R ratio was abnormal in 24% of patients. According to different diagnostic criteria of abnormal BP response to standing (>30 mmHg, >20 mmHg, and >10 mmHg fall in systolic BP), the frequency of abnormal results was 5.9%, 18% and 32%, respectively (p < 0.001). The frequency of feeling faint on standing was 18%, thus, it was identical with the prevalence of abnormal blood pressure response to standing when >20 mmHg fall in systolic blood pressure was considered as abnormal. Feeling faint on standing correlated significantly with both autonomic test results (p < 0.001). A fall >20 mmHg in systolic blood pressure after standing up seems to be the most reliable criterion for the assessment of orthostatic hypotension in the diagnosis of autonomic neuropathy in patients with Type 1 diabetes mellitus. 相似文献
1000.
Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Rac1 总被引:10,自引:0,他引:10 下载免费PDF全文
Clerk A Pham FH Fuller SJ Sahai E Aktories K Marais R Marshall C Sugden PH 《Molecular and cellular biology》2001,21(4):1173-1184
Small guanine nucleotide-binding proteins of the Ras and Rho (Rac, Cdc42, and Rho) families have been implicated in cardiac myocyte hypertrophy, and this may involve the extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and/or p38 mitogen-activated protein kinase (MAPK) cascades. In other systems, Rac and Cdc42 have been particularly implicated in the activation of JNKs and p38-MAPKs. We examined the activation of Rho family small G proteins and the regulation of MAPKs through Rac1 in cardiac myocytes. Endothelin 1 and phenylephrine (both hypertrophic agonists) induced rapid activation of endogenous Rac1, and endothelin 1 also promoted significant activation of RhoA. Toxin B (which inactivates Rho family proteins) attenuated the activation of JNKs by hyperosmotic shock or endothelin 1 but had no effect on p38-MAPK activation. Toxin B also inhibited the activation of the ERK cascade by these stimuli. In transfection experiments, dominant-negative N17Rac1 inhibited activation of ERK by endothelin 1, whereas activated V12Rac1 cooperated with c-Raf to activate ERK. Rac1 may stimulate the ERK cascade either by promoting the phosphorylation of c-Raf or by increasing MEK1 and/or -2 association with c-Raf to facilitate MEK1 and/or -2 activation. In cardiac myocytes, toxin B attenuated c-Raf(Ser-338) phosphorylation (50 to 70% inhibition), but this had no effect on c-Raf activity. However, toxin B decreased both the association of MEK1 and/or -2 with c-Raf and c-Raf-associated ERK-activating activity. V12Rac1 cooperated with c-Raf to increase expression of atrial natriuretic factor (ANF), whereas N17Rac1 inhibited endothelin 1-stimulated ANF expression, indicating that the synergy between Rac1 and c-Raf is potentially physiologically important. We conclude that activation of Rac1 by hypertrophic stimuli contributes to the hypertrophic response by modulating the ERK and/or possibly the JNK (but not the p38-MAPK) cascades. 相似文献