全文获取类型
收费全文 | 1898篇 |
免费 | 136篇 |
国内免费 | 2篇 |
出版年
2023年 | 26篇 |
2022年 | 20篇 |
2021年 | 54篇 |
2020年 | 43篇 |
2019年 | 41篇 |
2018年 | 40篇 |
2017年 | 42篇 |
2016年 | 51篇 |
2015年 | 70篇 |
2014年 | 120篇 |
2013年 | 169篇 |
2012年 | 84篇 |
2011年 | 119篇 |
2010年 | 81篇 |
2009年 | 94篇 |
2008年 | 111篇 |
2007年 | 107篇 |
2006年 | 100篇 |
2005年 | 70篇 |
2004年 | 85篇 |
2003年 | 62篇 |
2002年 | 45篇 |
2001年 | 19篇 |
2000年 | 20篇 |
1999年 | 42篇 |
1998年 | 23篇 |
1997年 | 14篇 |
1996年 | 12篇 |
1995年 | 21篇 |
1994年 | 17篇 |
1993年 | 25篇 |
1992年 | 19篇 |
1991年 | 22篇 |
1990年 | 20篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 12篇 |
1984年 | 20篇 |
1983年 | 15篇 |
1982年 | 12篇 |
1981年 | 4篇 |
1980年 | 11篇 |
1979年 | 8篇 |
1977年 | 8篇 |
1976年 | 7篇 |
1974年 | 6篇 |
1973年 | 5篇 |
1971年 | 3篇 |
排序方式: 共有2036条查询结果,搜索用时 15 毫秒
1.
目的:探讨心房钠尿钛ANP 在高血压心力衰竭发展过程中的变化和氨氯地平保护心肌细胞的作用。方法:对大鼠行腹主动
脉结扎术,术后随机选择40 只大鼠分为氨氯地平(中、高、低剂量)组以及模型组,另外选取10 只健康雄性SD 大鼠作为假手术
组。采用ELISA 方法检测各组血清ANP 浓度变化。结果:随着心功能不全加重,ANP 水平逐渐上升。氨氯地平用药组大鼠的心功
能改善明显优于模型组,ANP 明显降低,且随着氨氯地平用药量上升,心功能不断改善,ANP显著下降,P<0.05。结论:对血清
ANP浓度进行测定能够反映出高血压大鼠模型心室功能不全及充血性心力衰竭严重程度。而氨氯地平能够影响机体的ANP 分
泌对心肌细胞起到保护作用,从而有效抑制心室重构,延缓高血压心力衰竭疾病进展。 相似文献
2.
Naresh C. Bal Ashoke Sharon Subash C. Gupta Nivedita Jena Sana Shaikh Sandor Gyorke Muthu Periasamy 《The Journal of biological chemistry》2010,285(22):17188-17196
Calsequestrin undergoes dynamic polymerization with increasing calcium concentration by front-to-front dimerization and back-to-back packing, forming wire-shaped structures. A recent finding that point mutation R33Q leads to lethal catecholaminergic polymorphic ventricular tachycardia (CPVT) implies a crucial role for the N terminus. In this study, we demonstrate that this mutation resides in a highly conserved alternately charged residue cluster (DGKDR; cluster 1) in the N-terminal end of calsequestrin. We further show that this cluster configures itself as a ring system and that the dipolar arrangement within the cluster brings about a critical conformational flip of Lys31-Asp32 essential for dimer stabilization by formation of a H-bond network. We additionally show that Ca2+-induced calsequestrin aggregation is nonlinear and reversible and can regain the native conformation by Ca2+ chelation with EGTA. This study suggests that cluster 1 works as a molecular switch and governs the bidirectional transition between the CASQ2 monomer and dimer. We further demonstrate that mutations disrupting the alternating charge pattern of the cluster, including R33Q, impair Ca2+-CASQ2 interaction, leading to altered polymerization-depolymerization dynamics. This study provides new mechanistic insight into the functional effects of the R33Q mutation and its potential role in CPVT. 相似文献
3.
4.
A complete kinetic analysis of the forward mitochondrial creatine kinase reaction was conducted to define the mechanism for its rate enhancement when coupled to oxidative phosphorylation. Two experimental systems were employed. In the first, ATP was produced by oxidative phosphorylation. In the second, heart mitochondria were pretreated with rotenone and oligomycin, and ATP was regenerated by a phosphoenolpyruvate-pyruvate kinase system. Product inhibition studies showed that oxidative phosphorylation did not effect the binding of creatine phosphate to the enzyme. Creatine phosphate interacted competitively with both ATP and creatine, and the E · MgATP · CrP dead-end complex was not readily detected. In a similar manner, the dissociation constants for creatine were not influenced by the source of ATP: Kib = 29 mm; Kb = 5.3 mM, and the maximum velocity of the reaction was unchanged: V1 = 1 μmol/ min/mg. Slight differences were noted for the dissociation constant (Kia) of MgATP from the binary enzyme complex, E · MgATP. The values were 0.75 and 0.29 mm in the absence and presence of respiration. However, a 10-fold decrease in the steady-state dissociation constant (Ka) of MgATP from the ternary complex, E · MgATP · creatine, was documented: 0.15 mm with exogenous ATP and 0.014 mm with oxidative phosphorylation. Since Kia × Kb does not equal Ka × Kib under respiring conditions, the enzyme appears to be altered from its normal rapid-equilibrium random binding kinetics to some other mechanism by its coupling to oxidative phosphorylation. 相似文献
5.
Francis G. Spinale Rupak Mukherjee Juozas A. Zavadzkas Christine N. Koval Shenikqua Bouges Robert E. Stroud Lawrence W. Dobrucki Albert J. Sinusas 《The Journal of biological chemistry》2010,285(39):30316-30327
The membrane type-1 matrix metalloproteinase (MT1-MMP) is a unique member of the MMP family, but induction patterns and consequences of MT1-MMP overexpression (MT1-MMPexp), in a left ventricular (LV) remodeling process such as myocardial infarction (MI), have not been explored. MT1-MMP promoter activity (murine luciferase reporter) increased 20-fold at 3 days and 50-fold at 14 days post-MI. MI was then induced in mice with cardiac restricted MT1-MMPexp (n = 58) and wild type (WT, n = 60). Post-MI survival was reduced (67% versus 46%, p < 0.05), and LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT (41 ± 2 versus 32 ± 2%,p < 0.05). In the post-MI MT1-MMPexp mice, LV myocardial MMP activity, as assessed by radiotracer uptake, and MT1-MMP-specific proteolytic activity using a specific fluorogenic assay were both increased by 2-fold. LV collagen content was increased by nearly 2-fold in the post-MI MT1-MMPexp compared with WT. Using a validated fluorogenic construct, it was discovered that MT1-MMP proteolytically processed the pro-fibrotic molecule, latency-associated transforming growth factor-1 binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by 4-fold in the post-MI MT1-MMPexp group. Early and persistent MT1-MMP promoter activity occurred post-MI, and increased myocardial MT1-MMP levels resulted in poor survival, worsening of LV function, and significant fibrosis. A molecular mechanism for the adverse LV matrix remodeling with MT1-MMP induction is increased processing of pro-fibrotic signaling molecules. Thus, a proteolytically diverse portfolio exists for MT1-MMP within the myocardium and likely plays a mechanistic role in adverse LV remodeling. 相似文献
6.
Geoffrey P Dobson 《BBA》2002,1553(3):261-267
Our aim was to estimate a number of bioenergetic parameters in the beating mouse, rat and guinea pig heart in situ and compare the values to those in hearts of mammals over a 2000-fold range in body mass. For the mouse, rat and guinea pig heart, we report a phosphorylation ratio of 1005±50 (n=16), 460±32 (n=10) and 330±22 (n=5) mM−1 and a free cytosolic [ADP] concentration of 13, 18 and 22 μM, respectively. When each parameter was plotted against body mass, they scaled closely to the quarter power (−0.28, r=0.99 and −0.23, r=0.97). A similar regression slope was found when the inverse of free [ADP] was plotted against absolute mitochondrial (slope=−0.26, r=0.99) and myofibrillar volumes (slope=−0.24, r=0.99). The similar slopes indicate that the ratio of absolute mitochondria and myofibrillar volumes in the healthy mammalian heart is a constant, and independent of body size. In conclusion, our study supports the hypothesis that the mammalian heart has a number of highly conserved thermodynamic and kinetic parameters that obey quarter-power laws linking the phosphorylation ratio, ATP turnover rates, free [ADP] and absolute mitochondrial volumes to body size. The results are discussed in terms of possible mechanisms and potential deviations from these laws in some disease states. 相似文献
7.
Chronopathology of cardiovascular disease is now well documented. Silent myocardial ischaemia involves the same pathophysiological changes as conventional ischaemia. Early morning peaks in angina and myocardial ischaemia call for adequate timing of medication, β-blockers abolish the morning peak, and aspirin reduces morning infarctions. The effects of other antianginals on these phenomena are presently unknown. 相似文献
8.
H. J. G. Emons D. C. Groenenboom K. R. Westerterp W. H. M. Saris 《European journal of applied physiology and occupational physiology》1992,65(2):99-103
The aim of the present study was to compare data on 24-h energy expenditure (EE24h) in nine boys and ten girls (mean age 9.3 and 8.1 years, respectively) by heart rates (fc) combined with energy expenditure obtained from a 1-day stay in an indirect calorimeter (EEcal) and a 2-week period of normal living using the doubly labelled water method (EEdlw). Individual calibration curves were derived from fc and oxygen uptake measured during sleep (in the calorimeter), standing and walking on a treadmill. An estimation of energy expenditure based on 24-h fc monitoring (EEfc) was made during the stay in the calorimeter and on a normal school-day. Mean results showed an overestimation in EEfc compared to EEcal and EEdlw of 10.4% and 12.3% respectively, varying from 6.3% to 16.2%. These results confirmed earlier observations in adults that for a group the fc method overestimates EE24h by about 10%. 相似文献
9.
M. P. Rayson A. Davies D. G. Bell E. S. Rhodes-James 《European journal of applied physiology and occupational physiology》1995,71(5):405-408
Heart rate (beats · min–1;f
c) measured during marching with a load is often used to predict the oxygen cost (1·min–1; VO2) of the activity. The prediction comes from thef
c/VO2 relationship determined from laboratory measures off
c and VO2 during treadmill running. Studies in men have suggested that this may not be appropriate although this has yet to be examined in women. This study, therefore, compared thef
c/VO2 relationship between loaded marching and maximal running protocols in women. Sixteen female subjects [mean (SD), age 21.9 (2.3) years, height 6 (0.06) m, weight 62.6 (7.6) kg] had theirf
c (from three-lead chest electrodes) and VO2 measured first during standard treadmill run protocols, and again 1 week later during loaded marching protocols. The slopes and intercepts determined from linear regression off
c on VO2 for each individual for each protocol were compared as were the maximalf
c(f
cmax), VO2 and ratings of perceived exertion (RPE) from the last work period of each protocol in pairedt-tests. The VO2 slopes (P < 0.01) and intercepts (P < 0.05) differed significantly between loaded marching and running.f
cmax for loaded marching were 90% off
cmax for running (P < 0.01) and VO2 for loaded marching were 80% of those for running (P < 0.01). However, RPE at the final levels for the two protocols were not significantly different. The data suggest that in women the VO2 relationships for loaded marching and for running are different. This difference is similar to that found in men when speed is held constant and the load and gradient are varied. The results suggest that it would be erroneous to usef
c and VO2 measured during running protocols in the laboratory to estimate energy expenditure and work intensity during loaded marching in the filed. 相似文献
10.
B. L. Bennett R. D. Hagan K. A. Huey C. Minson D. Cain 《European journal of applied physiology and occupational physiology》1995,70(4):322-328
This study evaluated the effectiveness of a six-pack versus a four-pack cool vest in reducing heat strain in men dressed in firefighting ensemble, while resting and exercising in a warm/humid environment [34.4°C (day bulb), 28.9°C (wet bulb)]. Male volunteers (n = 12) were monitored for rectal temperature (T
re), mean skin temperature (T
sk), heart rate, and energy expenditure during three test trials: control (no cool vest), four-pack vest, and six-pack vest. The cool vests were worn under the firefighting ensemble and over Navy dungarees. The protocol consisted of two cycles of 30 min seated rest and 30 min walking on a motorized treadmill (1.12 m · s–1, 0% grade). Tolerance time for the control trial (93 min) was significantly less than both vest trials (120 min). Throughout heat exposure, energy expenditure varied during rest and exercise, but no differences existed among all trials (P > 0.05). During the first 60 min of heat exposure, physiological responses were similar for the four-pack and six-pack vests. However, during the second 60 min of heat exposure the six-pack vest had a greater impact on reducing heat strain than the four-pack vest. PeakT
e andT
sk at the end of heat exposure for 6-pack vest [mean (SD) 38.0(0.3)°C and 36.8(0.7)°C] were significantly lower compared to four-pack [38.6 (0.4)°C and 38.1(0.5)°C] and controls [38.9(0.5)°C and 38.4(0.5)°C]. Our findings suggest that the six-pack vest is more effective than the four-pack vest at reducing heat strain and improves performance of personnel wearing a firefighting ensemble. 相似文献