全文获取类型
收费全文 | 1250篇 |
免费 | 57篇 |
出版年
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 12篇 |
2018年 | 31篇 |
2017年 | 17篇 |
2016年 | 26篇 |
2015年 | 25篇 |
2014年 | 42篇 |
2013年 | 55篇 |
2012年 | 85篇 |
2011年 | 76篇 |
2010年 | 45篇 |
2009年 | 41篇 |
2008年 | 65篇 |
2007年 | 76篇 |
2006年 | 74篇 |
2005年 | 62篇 |
2004年 | 68篇 |
2003年 | 65篇 |
2002年 | 69篇 |
2001年 | 26篇 |
2000年 | 24篇 |
1999年 | 12篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 9篇 |
1994年 | 9篇 |
1993年 | 11篇 |
1992年 | 9篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 11篇 |
1984年 | 9篇 |
1983年 | 16篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1974年 | 8篇 |
1973年 | 12篇 |
1972年 | 8篇 |
1971年 | 6篇 |
1970年 | 6篇 |
1969年 | 12篇 |
1967年 | 7篇 |
排序方式: 共有1307条查询结果,搜索用时 171 毫秒
81.
Radács M Gálfi M Nagyéri G Molnár AH Varga C László F László FA 《Regulatory peptides》2008,148(1-3):1-5
The effects of adrenaline (A) and noradrenaline (NA) on vasopressin (VP) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP contents of the supernatant media were determined by radioimmunoassay after a 1 or 2-h incubation. Significantly increased VP levels were detected in the tissue culture media following the administration of A (an alpha+beta(2)-receptor agonist), depending on the dose of A. The VP secretion elevation was totally blocked by the previous administration of phentolamine (an alpha(1)+alpha(2)-receptor antagonist) or corynanthine (an alpha(1)-receptor antagonist). Yohimbine (an alpha(2)-receptor antagonist) did not influence the VP secretion increase induced by A. After the administration of NA (a beta+alpha(1)-receptor agonist), a VP secretion elevation was again detected, but the degree of enhancement proved smaller than that of the VP secretion increase induced by A. Propranolol (a beta(1)+beta(2)-receptor antagonist) before NA administration prevented the VP secretion increase. Atenolol (a beta(1)-receptor antagonist) did not block the VP secretion elevation induced by NA. Corynanthine (an alpha(1)-receptor antagonist) treatment before NA administration reduced the NA-induced VP enhancement, because NA has an alpha(1)-receptor agonist character in addition to its main character (a beta-receptor agonist). Surprisingly, the administration of pindolol (a beta(1)+beta(2)-receptor antagonist) enhanced VP secretion. This contradictory effect can be explained in that pindolol not only acts as a blocker, but also exerts "intrinsic sympathomimetic action" and a strong adrenergic agonist effect. Pindolol before NA administration significantly increased the NA-induced VP elevation. CONCLUSIONS: Mainly the alpha(1)- and beta(2)-adrenergic receptors are involved in the A- or NA-induced increase of VP secretion in isolated NH tissue cultures. The results indicate that VP release is influenced directly by the adrenergic system, and the adrenergic control of VP secretion from the NH tissue in rats can occur at the level of the posterior pituitary. 相似文献
82.
Miyazaki A Tsuda Y Fukushima S Yokoi T Vántus T Bökönyi G Szabó E Horváth A Kéri G Okada Y 《Bioorganic & medicinal chemistry letters》2008,18(23):6199-6201
Novel somatostatin analogues containing a pyrazinone ring, compounds 1 and 2, exhibited good antiproliferative activity on A431 tumor cells. To increase antitumor activity and binding affinity on somatostatin receptors (SSTRs), we substituted Tyr in the critical sequence, Tyr-D-Trp-Lys, with more hydrophobic aromatic residue. The substituted compounds dramatically lost antitumor activity, indicating that Tyr residue was an essential residue. 相似文献
83.
Sheets AR Fülöp P Derdák Z Kassai A Sabo E Mark NM Paragh G Wands JR Baffy G 《American journal of physiology. Gastrointestinal and liver physiology》2008,294(4):G1017-G1024
Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in beta-cells. Although UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to beta-cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum insulin levels and blunted lipid metabolic responses in fasted ucp2(-/-) mice, supporting the concept that UCP2 evolved to suppress insulin effects and to accommodate the fuel switch to fatty acids during starvation. In the absence of UCP2, fasting initially promotes peripheral lipolysis and hepatic fat accumulation at less than expected rates but culminates in protracted steatosis, indicating diminished hepatic utilization and clearance of fatty acids. We conclude that UCP2-mediated control of insulin secretion is a physiologically relevant mechanism of the metabolic response to fasting. 相似文献
84.
The discovery of nonsynaptic communication in the 1960s and 1970s was an important milestone in investigating the function of the nervous system, and it revolutionized our view about information transmission between neurons. In addition, nonsynaptic communication has a practical importance not only within the nervous system, but in the communication between the peripheral nervous system and other organ systems. Nonsynaptic communication takes place in different immune organs, which are innervated by sympathetic nerve terminals. In addition, the function of microglia, one of the immunocompetent cell types of the brain, can also be affected by neurotransmitters released from axon varicosities. The various functions of immune cells are modulated by released neurotransmitters without any direct synaptic contact between nerve endings and targeted immune cells requiring only functional neurotransmitter receptors on immune cells. Here, we briefly overview the role of the various receptor subtypes mediating nonsynaptic modulation of the function of immunocompetent cells both in the periphery and in the central nervous system. 相似文献
85.
Lacombe VA Viatchenko-Karpinski S Terentyev D Sridhar A Emani S Bonagura JD Feldman DS Györke S Carnes CA 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(5):R1787-R1797
Isolated diastolic dysfunction is found in almost half of asymptomatic patients with well-controlled diabetes and may precede diastolic heart failure. However, mechanisms that underlie diastolic dysfunction during diabetes are not well understood. We tested the hypothesis that isolated diastolic dysfunction is associated with impaired myocardial Ca(2+) handling during type 1 diabetes. Streptozotocin-induced diabetic rats were compared with age-matched placebo-treated rats. Global left ventricular myocardial performance and systolic function were preserved in diabetic animals. Diabetes-induced diastolic dysfunction was evident on Doppler flow imaging, based on the altered patterns of mitral inflow and pulmonary venous flows. In isolated ventricular myocytes, diabetes resulted in significant prolongation of action potential duration compared with controls, with afterdepolarizations occurring in diabetic myocytes (P < 0.05). Sustained outward K(+) current and peak outward component of the inward rectifier were reduced in diabetic myocytes, while transient outward current was increased. There was no significant change in L-type Ca(2+) current; however, Ca(2+) transient amplitude was reduced and transient decay was prolonged by 38% in diabetic compared with control myocytes (P < 0.05). Sarcoplasmic reticulum Ca(2+) load (estimated by measuring the integral of caffeine-evoked Na(+)-Ca(2+) exchanger current and Ca(2+) transient amplitudes) was reduced by approximately 50% in diabetic myocytes (P < 0.05). In permeabilized myocytes, Ca(2+) spark amplitude and frequency were reduced by 34 and 20%, respectively, in diabetic compared with control myocytes (P < 0.05). Sarco(endo)plasmic reticulum Ca(2+)-ATPase-2a protein levels were decreased during diabetes. These data suggest that in vitro impairment of Ca(2+) reuptake during myocyte relaxation contributes to in vivo diastolic dysfunction, with preserved global systolic function, during diabetes. 相似文献
86.
Neonatal single vitamin A (retinol; 3 mg) or vitamin D3 (cholecalciferol; 0.05 mg) treatment (imprinting) was done in male and female rats and 2 months later the endorphin, triiodothyronine (T3) and ACTH content of immune cells (peritoneal lymphocytes, monocyte-granulocyte-macrophage group [mo-gran], mast cells and thymic lymphocytes) were studied immunocytochemically by using flow cytometry and confocal microscopy. The T3 content was significantly decreased in peritoneal lymphocytes and in mo-gran and the endorphin content decreased in thymocytes of male animals, while ACTH was decreased in female lymphocytes and mo-gran. Vitamin D treatment was absolutely ineffective. The imprinting effects of vitamins A and D and their differences are discussed. The results call attention to the possible harmful effect of vitamin treatments during the perinatal critical period. 相似文献
87.
Parazzini M Ravazzani P Tognola G Thuróczy G Molnar FB Sacchettini A Ardesi G Mainardi LT 《Bioelectromagnetics》2007,28(2):122-129
In this study, 26 healthy young volunteers were submitted to 900 MHz (2 W) GSM cellular phone exposure and to sham exposure in separate sessions. The study was designed to assess cardiac regulatory mechanism in different autonomic nervous system (ANS) states during exposure to low-intensity EMF. Rest-to-stand protocol was applied to evaluate ANS in quiet condition (rest, vagal prevalence) and after a sympathetic activation (stand). The procedure is conducted twice in a double-blind design: once with a genuine EMF exposure and once with a sham exposure (at least 24 h apart). During each session three-leads electrocardiograms were recorded and RR series extracted off-line. Time domain and frequency domain HRV parameters were calculated in every phase of the protocol and during different exposures. The analysis of the data show there was no statistically significant effect due to EMF exposure both on main (i.e., RR mean) and most of the other HRV parameters. A weak interaction between some HRV parameters (i.e., SDNN, TINN, and triangular index in time domain and LF power in frequency domain analysis) and RF exposure was observed and this effect seems to be gathered around the sympathetic response to stand. 相似文献
88.
Vegh MG Kovács AD Kovács G Szabó G Tihanyi K Hársing LG Lévay G 《Neurochemistry international》2007,50(3):555-563
We observed in vitro neuroprotective and AMPA/kainate receptor antagonist effects of the new 2,3-benzodiazepine derivative EGIS-8332 (R,S-1-(4-aminophenyl)-7,8-methylenedioxy-4-cyano-4-methyl-3-N-acetyl-5H-3,4-dihydro-2,3-benzodiazepine) using the lactate dehydrogenase (LDH) release assay and patch clamp recordings on primary cultures of rat embryonic telencephalon neurons exposed to AMPA/kainate receptor agonists. EGIS-8332 potently decreased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate induced LDH release (IC(50)=5.2+/-0.4 and 7.4+/-1.3 microM, respectively) from the cells. Whole-cell patch clamp studies carried out on the ionotropic glutamate receptors N-methyl D-aspartate (NMDA), as well as AMPA (and kainate) in cultured telencephalon neurons verified that EGIS-8332 blocked steady state responses to AMPA and kainate (IC(50)=1.7+/-0.4 and 6.2+/-1.6 microM, respectively), but hardly influenced currents evoked by NMDA. EGIS-8332 also inhibited kainate-evoked response in CHO cells expressing the flop variant of GluR1 receptor and, in cerebellar Purkinje cells at similar efficiency. The stereoselectivity of the inhibitory site is established by the clearly dissimilar inhibitory potency of the enantiomer components of EGIS-8332 differing in the configuration of methyl and cyano substituents on carbon C(4): the R(-) enantiomer was found to be the efficient species. This finding suggests that the inhibitory interaction between the channel protein and drug is promoted by presence of the C(4) methyl group. The inhibition of the AMPA/kainate ion channels by EGIS-8332 is non-competitive, not use dependent, and depends neither on the closed/open state of the channel, nor the membrane potential. These findings suggest an allosteric mechanism for the inhibition. These in vitro observations suggest that the compound might be useful in the treatments of certain acute and chronic neurological syndromes initiated by derangements of ionotropic glutamate receptor function. 相似文献
89.
Iron homeostasis in chronic inflammation 总被引:1,自引:0,他引:1
Inflammation induced anemia and resistance to erythropoietin are common features in patients with chronic kidney disease (CKD). Elevated levels of cytokines and enhanced oxidative stress, conditions associated with inflammatory states, are implicated in the development of anemia. Accumulating evidence suggests that activation of cytokine cascade and the associated acute-phase response, as it often occurs in patients with CKD, divert iron from erythropoiesis to storage sites within the reticuloendothelial system leading to functional iron deficiency and subsequently to anemia or resistance to erythropoietin. Other processes have also been shown to be involved in the pathogenesis of anemia provoked by the activated immune system including an inhibition of erythroid progenitor proliferation and differentiation, a suppression of erythropoietin production and a blunted response to erythropoietin. The present review concerns the underlying alterations in iron metabolism induced by chronic inflammation that result in anemia. 相似文献
90.