全文获取类型
收费全文 | 2416篇 |
免费 | 112篇 |
国内免费 | 60篇 |
出版年
2023年 | 31篇 |
2022年 | 27篇 |
2021年 | 35篇 |
2020年 | 47篇 |
2019年 | 46篇 |
2018年 | 43篇 |
2017年 | 53篇 |
2016年 | 34篇 |
2015年 | 50篇 |
2014年 | 96篇 |
2013年 | 130篇 |
2012年 | 99篇 |
2011年 | 165篇 |
2010年 | 95篇 |
2009年 | 91篇 |
2008年 | 109篇 |
2007年 | 108篇 |
2006年 | 103篇 |
2005年 | 73篇 |
2004年 | 72篇 |
2003年 | 75篇 |
2002年 | 76篇 |
2001年 | 43篇 |
2000年 | 45篇 |
1999年 | 44篇 |
1998年 | 37篇 |
1997年 | 42篇 |
1996年 | 38篇 |
1995年 | 39篇 |
1994年 | 41篇 |
1993年 | 40篇 |
1992年 | 46篇 |
1991年 | 35篇 |
1990年 | 33篇 |
1989年 | 42篇 |
1988年 | 29篇 |
1987年 | 30篇 |
1986年 | 40篇 |
1985年 | 41篇 |
1984年 | 55篇 |
1983年 | 41篇 |
1982年 | 38篇 |
1981年 | 38篇 |
1980年 | 23篇 |
1979年 | 18篇 |
1978年 | 10篇 |
1977年 | 14篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1973年 | 6篇 |
排序方式: 共有2588条查询结果,搜索用时 15 毫秒
831.
832.
Schreiber S Garten D Nguyen TH Konradt M Bücker R Scheid P 《Cell and tissue research》2007,329(2):313-320
The gastric H+/K+-ATPase is located within an infolding (secretory canaliculus) of the apical plasma membrane of gastric parietal cells. Our
aim was to measure the pH values in the cytosol and canaliculus of the acid-secreting parietal cell and the adjacent gland
lumen in situ. We used ultrafine double-barreled tip-sealed microelectrodes at high acceleration rates for intracellular and
canalicular measurements. Immunohistochemical staining of the parietal cells was used to identify the track of the electrode
and to estimate the position of the electrode tip at the time of the last intracellular measurement. En route to the deepest
regions of the mucosa, where the average gland lumen pH was approximately 3, and on advancing in steps of 2 μm, the electrode
entered the cytosol of the parietal cells, where the pH value was 7.4. Advancing the electrode further resulted, in several
instances, in a sharp decrease in pH to an average value of 1.7 ± 0.2, which we interpreted as the measurement within the
canaliculus. When the electrode was advanced even further, the pH reading returned to the cytosolic value. From the difference
in pH between the secreting canaliculus and the adjacent gland lumen, we concluded that the released acid was immediately
buffered. Thus, the only cellular structure directly exposed to the highly acidic canalicular content is the apical membrane
forming the canaliculus in the parietal cell. 相似文献
833.
Daosukho C Chen Y Noel T Sompol P Nithipongvanitch R Velez JM Oberley TD St Clair DK 《Free radical biology & medicine》2007,42(12):1818-1825
Cardiac injury is a major complication for oxidative-stress-generating anticancer agents exemplified by Adriamycin (ADR). Recently, several histone deacetylase inhibitors (HDACIs) including phenylbutyrate (PBA) have shown promise in the treatment of cancer with little known toxicity to normal tissues. PBA has been shown to protect against oxidative stress in normal tissues. Here, we examined whether PBA might protect heart against ADR toxicity in a mouse model. The mice were i.p. injected with ADR (20 mg/kg). PBA (400 mg/kg/day) was i.p. injected 1 day before and daily after the ADR injection for 2 days. We found that PBA significantly decreased the ADR-associated elevation of serum lactate dehydrogenase and creatine kinase activities and diminished ADR-induced ultrastructual damages of cardiac tissue by more than 70%. Importantly, PBA completely rescued ADR-caused reduction of cardiac functions exemplified by ejection fraction and fraction shortening, and increased cardiac manganese superoxide dismutase (MnSOD) protein and activity. Our results reveal a previously unrecognized role of HDACIs in protecting against ADR-induced cardiac injury and suggest that PBA may exert its cardioprotective effect, in part, by the increase of MnSOD. Thus, combining HDACIs with ADR could add a new mechanism to fight cancer while simultaneously decrease ADR-induced cardiotoxicity. 相似文献
834.
835.
Yong SL Ni Y Zhang T Tester DJ Ackerman MJ Wang QK 《Biochemical and biophysical research communications》2007,352(2):378-383
The N(1325)S mutation in the cardiac sodium channel gene SCN5A causes the type-3 long-QT syndrome but the arrhythmogenic trigger associated with N(1325)S has not been characterized. In this study, we investigated the triggers for cardiac events in the expanded N(1325)S family. Among 11 symptomatic patients with document triggers, six died suddenly during sleep or while sitting (bradycardia-induced trigger), three died suddenly, and two developed syncope due to stress and excitement (non-bradycardia-induced). Patch-clamping studies revealed that the late sodium current (I(Na,L)) generated by mutation N(1325)S in ventricular myocytes from TG-NS/LQT3 mice was reduced with increased pacing, which explains bradycardia-induced mortalities in the family. The non-bradycardic triggers are related to the finding that APD became prolonged and unstable at increasing rates, often with alternating repolarization phases which was corrected with verapamil. This implies that Ca2+ influx and intracellular Ca2+ ([Ca2+]i) ions are involved and that [Ca2+]i inhomogeneity may be the underlying mechanisms behind non-bradycardia LQT3 arrhythmogenesis associated with mutation N(1325)S. 相似文献
836.
Olga Gavrilova 《生物化学与生物物理学报:生物膜》2007,1768(9):2070-2077
To determine which efflux carriers are involved in hepatic phalloidin elimination, hepatobiliary [3H]-demethylphalloin (DMP) excretion was studied in normal Wistar rats and in Mrp2 deficient TR(−) Wistar rats as well as in normal wild-type FVB mice, Mdr1a,b(−/−) knockout mice, and Bcrp1(−/−) knockout mice by in situ bile duct/gallbladder cannulation. A subtoxic dose of 0.03 mg DMP/kg b.w. was used, which did not induce cholestasis in any tested animal. Excretion of DMP into bile was not altered in Mdr1a,b(−/−) mice or in Bcrp1(−/−) mice compared with wild-type FVB mice. Whereas 17.6% of the applied dose was excreted into bile of normal Wistar rats, hepatobiliary excretion decreased to 7.9% in TR(−) rats within 2 h after intravenous application. This decrease was not due to reduced cellular DMP uptake, as shown by normal expression of Oatp1b2 in livers of TR(−) rats and functional DMP uptake into isolated TR(−) rat hepatocytes. Tissue concentrations of phalloidin were also not altered in any of the transgenic mice. Interestingly, the decrease of biliary DMP excretion in the TR(−) rats was not followed by any increase of phalloidin accumulation in the liver but yielded a compensatory excretion of the toxin into urine, indicating that hepatocytes of TR(−) rats expelled phalloidin back into blood circulation. 相似文献
837.
Phase diagrams of 3-component lipid bilayer mixtures containing cholesterol reveal major differences among the different types of lipids. Here we report that mixtures of cholesterol together with POPC and a high-melting temperature PC or sphingomyelin show different phase behavior from similar mixtures that contain DOPC or di-phytanoyl-PC instead of POPC. In particular, only one region of macroscopic phase coexistence occurs with POPC, a region of coexisting liquid disordered and solid phases, {Lα + Lβ}. Fluorescence microscopy imaging is useful for these studies, but is subject to artifactual light-induced domain formation, as reported by Ayuyan and Cohen [A.G. Ayuyan, F.S. Cohen, Lipid peroxides promote large rafts: Effects of excitation of probes in fluorescence microscopy and electrochemical reactions during vesicle formation, Biophys. J. 91 (2006) 2172-2183.]. This artifact can be attenuated by decreased illumination and low dye concentration. The use of the free radical scavenger n-propyl gallate can reduce the artifact, but this molecule enters the bilayer and itself perturbs the phase behavior. We suggest that the light-induced domain separation artifact might actually arise from pre-existing lipid clusters that are induced to coalesce, and therefore indicates highly nonrandom mixing of the lipid components. 相似文献
838.
A 900-MHz NMR study is reported of peptide sMTM7 that mimics the cytoplasmic proton hemi-channel domain of the seventh transmembrane segment (TM7) from subunit a of H+-V-ATPase from Saccharomyces cerevisiae. The peptide encompasses the amino acid residues known to actively participate in proton translocation. In addition, peptide sMTM7 contains the amino acid residues that upon mutation cause V-ATPase to become resistant against the inhibitor bafilomycin. 2D TOCSY and NOESY 1H-1H NMR spectra are obtained of sMTM7 dissolved in d6-DMSO and are used to calculate the three-dimensional structure of the peptide. The NMR-based structures and corresponding dynamical features of peptide sMTM7 show that sMTM7 is composed of two α-helical regions. These regions are separated by a flexible hinge of two residues. The hinge acts as a ball-and-joint socket and both helical segments move independently with respect to one another. This movement in TM7 is suggested to cause the opening and closing of the cytoplasmic proton hemi-channel and enables proton translocation. 相似文献
839.
840.
The objective of this study is to investigate the impact of trauma on erythrocyte caused by long term in vitro pumping using roller pump. Ten bags of human blood (400 ml each) were provided by a local blood bank and they were divided into two groups with five bags in each group. Each blood bag was subject to pumping in a closed circuit, which was composed of silica gel tubes and a roller pump. Polystan and COBE pumps were used for the two groups, respectively. The blood was pumped for 16 h in vitro. Free hemoglobin (FHb), platelets (PLT), erythrocyte fragility (EF), and morphological analysis of erythrocytes observed under scanning electron microscope were measured to evaluate the impact of trauma on erythrocytes. A small amount of blood was collected for analysis before pumping, at the end of the 4th hour and then every 2 h till the end of the 16th hour. Some blood samples were also collected for electron microscope scanning before pumping and every 4 h during pumping. It was found that FHb and PLT linearly increased with the pumping time. There was a significant correlation between the two parameters (r=0.7745, p<0.001). The hemolysis indexes of the two groups were 0.296 and 0.3993 mg/L/h, respectively, with no significant difference. During the pumping process, EF changed slightly. The observation of scanning electron microscopy showed various deformed erythrocytes after pumping, including the distortion of cell membrane and the appearance of echinocytes, which increased with pumping time. This study demonstrated that long term pumping using roller pump not only caused the immediate rupture of red blood cells, i.e. the immediate hemolysis, but also caused sub-trauma to a large number of erythrocytes, which led to the delayed hemolysis. The change of erythrocyte morphology was the basis of the delayed hemolysis. 相似文献