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71.
Liao P Yu D Li G Yong TF Soon JL Chua YL Soong TW 《The Journal of biological chemistry》2007,282(48):35133-35142
Native smooth muscle L-type Ca(v)1.2 calcium channels have been shown to support a fraction of Ca(2+) currents with a window current that is close to resting potential. The smooth muscle L-type Ca(2+) channels are also more susceptible to inhibition by dihydropyridines (DHPs) than the cardiac channels. It was hypothesized that smooth muscle Ca(v)1.2 channels exhibiting hyperpolarized shift in steady-state inactivation would contribute to larger inhibition by DHP, in addition to structural differences of the channels generated by alternative splicing that modulate DHP sensitivities. In addition, it has also been shown that alternative splicing modulates DHP sensitivities by generating structural differences in the Ca(v)1.2 channels. Here, we report a smooth muscle L-type Ca(v)1.2 calcium channel splice variant, Ca(v)1.2SM (1/8/9(*)/32/Delta33), that when expressed in HEK 293 cells display hyperpolarized shifts for steady-state inactivation and activation potentials when compared with the established Ca(v)1.2b clone (1/8/9(*)/32/33). This variant activates from more negative potentials and generates a window current closer to resting membrane potential. We also identified the predominant cardiac isoform Ca(v)1.2CM clone (1a/8a/Delta9(*)/32/33) that is different from the established Ca(v)1.2a (1a/8a/Delta9(*)/31/33). Importantly, Ca(v)1.2SM channels were shown to be more sensitive to nifedipine blockade than Ca(v)1.2b and cardiac Ca(v)1.2CM channels when currents were recorded in either 5 mM Ba(2+) or 1.8 mM Ca(2+) external solutions. This is the first time that a smooth muscle Ca(v)1.2 splice variant has been identified functionally to possess biophysical property that can be linked to enhanced state-dependent block by DHP. 相似文献
72.
Down-regulation of mitofusin-2 expression in cardiac hypertrophy in vitro and in vivo 总被引:2,自引:0,他引:2
Mitofusin-2 (Mfn2) suppresses smooth muscle cell proliferation through inhibition of the Ras-extracellular signal-regulated kinases (ERK1/2) pathway. Since the ERK1/2 pathway is implicated in mediating hypertrophic signaling, we studied the changes in Mfn2 in cardiac hypertrophy using in vitro and in vivo models. Phenylephrine was used to induce hypertrophy in neonatal rat ventricular myocytes (NRVMs). In vivo hypertrophy models included spontaneously hypertensive rats (SHR), pressure-overload hypertrophy by transverse aortic constriction (TAC), hypertrophy of non-infarcted myocardium following myocardial infarction (MI), and cardiomyopathy due to cardiac-restricted overexpression of beta(2)-adrenergic receptors (beta(2)-TG). We determined hypertrophic parameters and analysed expression of atrial natriuretic peptide (ANP) and Mfn2 by real-time PCR. Phosphorylated-ERK1/2 (phospho-ERK) was measured by Western blot. Mfn2 was downregulated in phenylephrine treated NRCMs (by approximately 40%), hypertrophied hearts from SHR (by approximately 80%), mice with TAC (at 1 and 3 weeks, by approximately 50%), and beta(2)-TG mice (by approximately 20%). However, Mfn2 was not downregulated in hypertrophied hearts with 15 weeks of TAC, nor in hypertrophied non-infarcted myocardium following MI. phospho-ERK1/2 was increased in hypertrophied myocardium at 1 week post-TAC, but not in non-infarcted myocardium after MI, indicating that downregulated Mfn2 may be accompanied by an increase of phospho-ERK1/2. This study shows, for the first time, downregulated Mfn2 expression in hypertrophied hearts, which depends on the etiology and time course of hypertrophy. Further study is required to examine the causal relationship between Mfn2 and cardiac hypertrophy. 相似文献
73.
74.
Predicting the wetland distributions under climate warming in the Great Xing’an Mountains,northeastern China 总被引:1,自引:0,他引:1
Hongjuan Liu Rencang Bu Jintong Liu Wenfang Leng Yuanman Hu Libing Yang Huitao Liu 《Ecological Research》2011,26(3):605-613
The wetland ecosystem is particularly vulnerable to hydrological and climate changes. The Great Xing’an Mountain is such a
region in China that has a large area of wetlands with rare human disturbance. The predictions of the global circulation model
CGCM3 (the third-generation coupled global climate model from the Canadian Centre for Climate Modeling and Analysis) indicated
that the temperature in The Great Xing’an Mountain will rise by 2–4°C over the next 100 years. This paper predicts the potential
distributions of wetlands in this area under the current and warming climate conditions. This predication was performed by
the Random Forests model, with 18 environmental variables, which will reflect the climate and topography conditions. The model
has been proven to have a great prediction ability. The wetland distributions are primarily topography-driven in the Great
Xing’an Mountains. Mean annual temperature, warmness index, and potential evapotranspiration ratio are the most important
climatic factors in wetland distributions. The model predictions for three future climate scenarios show that the wetland
area tends to decrease, and higher emission will also cause more drastic shrinkage of wetland distributions. About 30% of
the wetland area will disappear by 2050. The area will decrease 62.47, 76.90, and 85.83%, respectively, under CGCM3-B1, CGCM3-A1B,
and CGCM3-A2 by 2100. As for spatial allocation, wetlands may begin to disappear from the sides to the center and south to
north under a warming climate. Under CGCM3-B1, the loss of wetlands may mainly occur in the south hills with flatter terrain,
and some may occur in the north hills and intermontane plains. Under CGCM3-A1B, severe vanish of wetlands is predicted. Under
CGCM3-A2, only a small area of wetlands may remain in the north of the high mountains. 相似文献
75.
Although MDM2 is known to be a critical negative regulator of p53, MDM2 only catalyzes p53 mono- or multiple monoubiquitination in vitro and in vivo, which is insufficient for the initiation of proteasomal degradation. MDM2 does not polyubiquitinate p53 in vitro, however, which indicates that the activity of other ubiquitin ligase(s) or cofactor(s) is required for MDM2-mediated p53 polyubiquitination and degradation. In our recent study, we demonstrated that UBE4B, an E3 and E4 ubiquitin ligase with a U-box domain, interacts physically with both p53 and MDM2. Our findings revealed that UBE4B negatively regulates the level of p53 and inhibits p53-dependent transactivation and apoptosis. We propose that inhibition of MDM2 binding to UBE4B may provide another approach to inhibit MDM2 E3 ligase activity for tumor suppressor p53. It could lead to novel anticancer therapies, with the possibility of reducing the public health burden from cancer.Key words: ubiquitination, MDM2, UBE4B, p53, degradation 相似文献
76.
77.
78.
Carnoy's No. 2 fluid (absolute alcohol-glacial acetic acid-chloroform) modified by saturation with mercuric chloride was found to be an effective killing and fixing agent for microsporocytes of Trifolium pratense, T. incarnatum, T. repens, T. hybridum, and Glycine max. Microsporocytes so fixed were softened in a 0.1N HCl solution at 45°C. for approximately 10 minutes, then smeared by die standard aceto-carmine technic. The modifications enabled chromosome counts to be made successfully in microsporocyte smears, whereas satisfactory smears could not be made when standard technics of killing and fixing were used. 相似文献
79.
80.
冲击波负压对大鼠肺致伤效应的初步观察 总被引:5,自引:0,他引:5
观察了不同的冲击波负压峰值对大鼠肺的影响。各种条件下的冲击波负压值可由负压发生装置来模拟调节,这种装置可满足化爆、核爆和爆炸性减压下负压参数的一般要求,参数稳定,重复性好。冲击波负压峰值范围为-13~-90kPa,下降时间为1~90ms,持续时间为14~2 000ms。6组Wistar系大鼠,分别暴露在-47.2~-84.0kPa的冲击波负压环境中,伤后立即解剖动物,重点观察肺伤情。实验结果显示,在上述冲击波负压环境中,肺可出现从无伤至极重度伤;出血、充血以及肺表面压痕酷似肺冲击伤的病理表现。随着冲击波负压峰值的变化,各组肺伤情亦随着变化,冲击波负压峰值(△P)和减压倍数(P_i/P_a)分别与肺出血面积和动物死亡率相关显著或非常显著。本实验提示,一定条件下的冲击波负压具有明显的致伤作用,且伤情变化范围与超压所致肺伤情变化范围相同,超压和冲击波负压在一定条件下可通过伤情指标等效。 相似文献