全文获取类型
收费全文 | 6352篇 |
免费 | 685篇 |
国内免费 | 2篇 |
出版年
2022年 | 45篇 |
2021年 | 99篇 |
2020年 | 53篇 |
2019年 | 59篇 |
2018年 | 76篇 |
2017年 | 75篇 |
2016年 | 125篇 |
2015年 | 278篇 |
2014年 | 232篇 |
2013年 | 312篇 |
2012年 | 447篇 |
2011年 | 418篇 |
2010年 | 253篇 |
2009年 | 190篇 |
2008年 | 305篇 |
2007年 | 322篇 |
2006年 | 269篇 |
2005年 | 295篇 |
2004年 | 318篇 |
2003年 | 256篇 |
2002年 | 257篇 |
2001年 | 103篇 |
2000年 | 99篇 |
1999年 | 76篇 |
1998年 | 112篇 |
1997年 | 60篇 |
1996年 | 67篇 |
1995年 | 60篇 |
1994年 | 64篇 |
1993年 | 48篇 |
1992年 | 102篇 |
1991年 | 82篇 |
1990年 | 84篇 |
1989年 | 91篇 |
1988年 | 73篇 |
1987年 | 63篇 |
1986年 | 78篇 |
1985年 | 72篇 |
1984年 | 87篇 |
1983年 | 64篇 |
1982年 | 73篇 |
1981年 | 52篇 |
1980年 | 59篇 |
1979年 | 62篇 |
1978年 | 49篇 |
1977年 | 63篇 |
1974年 | 53篇 |
1972年 | 48篇 |
1971年 | 46篇 |
1969年 | 41篇 |
排序方式: 共有7039条查询结果,搜索用时 15 毫秒
61.
Control of stimulus-secretion coupling in adrenal medullary chromaffin cells by microfilament-specific macromolecules 总被引:2,自引:0,他引:2
J E Friedman P I Lelkes K Rosenheck A Oplatka 《The Journal of biological chemistry》1986,261(13):5745-5750
We have incorporated the myosin fragment heavy meromyosin (HMM), which is known to interact mechanochemically and enzymatically with actin filaments, into intact chromaffin cells of the bovine adrenal medulla, in order to study the possible involvement of actin and myosin in stimulus-secretion coupling. HMM was found to stimulate secretion of catecholamines, to cause depolarization of the plasma membrane, and to enhance 22Na+ uptake. HMM-stimulated catecholamine secretion was dependent on the presence of extracellular Na+. The Na+ uptake caused by HMM was inhibited by 10 microM amiloride. Acetylcholine-stimulated catecholamine secretion and 22Na+ uptake were both enhanced by HMM incorporation. A Na+/H+ antiporter, activated by the interaction of HMM with the cells' microfilaments, seems to be involved in HMM action and could possibly also be a component of stimulus-secretion coupling in chromaffin cells, induced by regular agonists. 相似文献
62.
Increased 5-Hydroxytryptamine and Norepinephrine Release from Rat Brain Slices by the Red Sea Flatfish 总被引:1,自引:1,他引:0
The effect of the Red Sea flatfish toxin pardaxin was examined on K+-evoked and on basal release of either [3H]norepinephrine or [3H]5-hydroxytryptamine from preloaded rat cortical slices. The K+-induced release of the neurotransmitters was stimulated in a dose-related manner at concentrations ranging from 0.5 to 4 micrograms/ml. Basal release of the two transmitters was elevated to a lesser extent. Although the stimulation of evoked release was approximately equivalent for the two neurotransmitters, the response to 5-hydroxytryptamine was reversible whereas that of norepinephrine was not washed by 20 min of superfusion. The mechanisms involved in producing these actions of pardaxin are not known; however, they may be mediated by changes in electrolyte fluxes across the neuronal membranes. 相似文献
63.
Philip Skehan James E. Thomas Susan J. Friedman 《In vitro cellular & developmental biology. Plant》1986,22(11):632-636
Summary Sarcoma 180 monolayers spontaneously shed single cells and small multicellular aggregates into the surrounding medium to produce
a dual population of floating and substratum-attached cells. Shedding was a motility-associated event that occurred when cells
attempted to migrate over one another. It resulted from a combination of cell shape change and active motility, which increased
sensitivity to fluid shear dislodgement by reducing a cell's surface area of adhesive contact and increasing strain tension
at its adhesive contact points. Shedding occurred at all phases of the cell cycle. Extracellular matrix but not conditioned
medium enhanced the floating subpopulation by slowing the kinetics of rattachment to plastic and cellular substrata. Although
sarcoma 180 cells are anchorage independent in the sense that they grow readily in single cell suspension, they nevertheless
exhibited anchorage modulation of their cell cycle. Short periods in suspension produced a mild G1 accumulation, whereas longer periods of anchorage deprivation led to a mild G2 accumulation which appeared to result from an interference with cytokinesis.
This work was supported by grants from the Medical Research Council of Canada, The National Cancer Institute of Canada, the
Alberta Heritage Savings and Trust Fund for Applied Cancer Research, and the Alberta Heritage Fund for Medical Research. 相似文献
64.
P W Davenport W A Friedman F J Thompson O Franzén 《Journal of applied physiology》1986,60(6):1843-1848
It has long been recognized that humans can perceive respiratory loads. There have been several studies on the detection and psychophysical quantification of mechanical load perception. This investigation was designed to record cortical sensory neurogenic activity related to inspiratory mechanical loading in humans. Inspiration was periodically occluded in human subjects while the electroencephalographic (EEG) activity in the somatosensory region of the cerebral cortex was recorded. The onset of inspiratory mouth pressure (Pm) was used to initiate signal averaging of the EEG signals. Cortical evoked potentials elicited by inspiratory occlusions were observed when C3 and C alpha were referenced to CZ. This evoked potential was not observed with the control (unoccluded) breaths. There was considerable subject variability in the peak latencies that was related to the differences in the inspiratory drive, as measured by occlusion pressure (P0.1). The results of this study demonstrate that neurogenic activity can be recorded in the somatosensory region of the cortex that is related to inspiratory occlusions. The peak latencies are longer than analogous somatosensory evoked potentials elicited by stimulation of the hand and foot. It is hypothesized that a portion of this latency difference is related to the time required for the subject to generate sufficient inspiratory force to activate the afferents mediating the cortical response. 相似文献
65.
T Chajek-Shaul G Friedman H Knobler O Stein J Etienne Y Stein 《Biochimica et biophysica acta》1985,837(2):123-134
Lipoprotein lipase synthesized by cultured rat preadipocytes is present in three compartments: an intracellular, a surface-related 3-min heparin-releasable, and that secreted into the culture medium. 30 min after addition of 6 microM monensin, the lipoprotein lipase activity in the heparin-releasable compartment starts to decrease; by 4 h of monensin treatment the lipoprotein lipase activity in the heparin-releasable pool and in the culture medium is about 10% of that found in control dishes. The intracellular activity, which had been identified as lipoprotein lipase by an antiserum to lipoprotein lipase, increases slowly and doubles by 24 h. However, since the cellular compartment accounts for 10-25% of total activity, this increase does not account for the missing enzyme activity. To determine whether this enzyme molecule is synthesized but is not active, incorporation of labeled leucine, mannose and galactose into immunoadsorbable lipoprotein lipase was studied in control, monensin- or tunicamycin-treated cells. Addition of tunicamycin (5 micrograms/ml) for 24 h caused a 30-50% reduction in immunoadsorbable lipoprotein lipase, but the enzyme activity was reduced by 90%. On the other hand, 4 h monensin treatment reduced both incorporation of [3H]leucine into immunoadsorbable lipoprotein lipase and heparin-releasable and medium lipoprotein lipase activity by 57 to 77%. The immunoadsorbable lipoprotein lipase in the intracellular compartment has a [14C]mannose to [3H]galactose ratio of 0.15 and this ratio increased 6-fold in monensin-treated cells. The intracellular lipoprotein lipase in monensin-treated cells had the same affinity for both the native and synthetic substrate as the lipoprotein lipase in control cells, yet its spontaneous secretion into the culture medium and its release by 3 min heparin treatment was markedly decreased. The present results indicate that: the presence of asparagine-linked oligosaccharide (formation of which is inhibited by tunicamycin) is mandatory for the expression of lipoprotein lipase activity; lipoprotein lipase is active also in a high mannose form; and terminal glycosylation and oligosaccharide processing, which is inhibited by monensin, may be important for the appearance of heparin-releasable lipoprotein lipase and secretion of lipoprotein lipase into the medium. 相似文献
66.
Metabolism and Solubilization of Cellulose by Clostridium cellulolyticum H10 总被引:9,自引:2,他引:7
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
When Clostridium cellulolyticum was grown with cellulose MN300 as the substrate, the rates of growth and metabolite production were found to be lower than those observed with soluble sugars as the substrate. At low cellulose concentrations, the growth yields were equal to those obtained with cellobiose. The main fermentation products from cellulose and soluble sugars were the same. Up to 15 mM of consumed hexose, a change in the metabolic pathway favoring lactate production similar to that observed with soluble sugars was found to occur concomitantly with a decrease in molar growth yield. With cellulose concentrations above 5 g/liter, accumulation of soluble sugars occurred once growth had ceased. Glucose accounted for 30% of these sugars. A kinetic analysis of cellulose solubilization revealed that cellulolysis by C. cellulolyticum involved three stages whatever cellulose concentration was used. Analysis of these kinetics showed three consecutive enzymatic activity levels having the same Km (0.8 g of cellulose per liter, i.e., 5 mM hexose equivalent) but decreasing values of Vmax. The hypothesis is suggested that each step corresponds to differences in cellulose structure. 相似文献
67.
The effects of ozone on lung arachidonate metabolism in-vitro were studied in cultured bovine pulmonary endothelial cells exposed for 2 hours to ozone in concentrations up to 1.0 ppm. A concentration-dependent decrease in prostacyclin synthesis was found (90% decrease at the highest ozone level of 1.0 ppm). The inhibition of prostacyclin synthesis was not due to a decreased release of arachidonic acid from membrane lipids. We also examined the hypoxic pulmonary vasoconstrictive response to 10% oxygen inhalation in anesthetized dogs in-vivo after exposure to 1.0 ppm ozone for 1 hour. Pulmonary vascular resistance was significantly increased after ozone exposure, similar to the findings in dogs given indomethacin (15 mg/kg). The percentage change in the hypoxic pulmonary pressor response was similar between the ozone exposure and indomethacin-treated groups, although due to the variance of the pulmonary vascular resistance values during hypoxia the results did not reach statistical significance. These results suggest that ozone inhalation affects pulmonary endothelial arachidonate metabolism in-vivo as well as in-vitro. 相似文献
68.
Epitope-relatedness and phenotyping of hepatic cytochromes P-450 with monoclonal antibodies. 总被引:1,自引:1,他引:0
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The epitope-specific cytochrome P-450 content of animal livers was analysed by radioimmunoassay using a panel of seven monoclonal antibodies (MAbs) made to a 3-methylcholanthrene-induced rat liver cytochrome P-450. Competitive radioimmunoassays utilizing a reference radiolabelled MAb and a series of unlabelled MAbs indicated that there are at least three distinct classes of MAbs to different epitopes on cytochrome P-450. In addition, a direct radioimmunoassay employing a radiolabelled second antibody detected MAb-specific cytochromes P-450 in livers from different animals. This radioimmunoassay detected large elevations in the levels of these cytochromes P-450 in the livers of 3-methylcholanthrene-treated rats and C57BL/6 mice compared with untreated rats, 3-methylcholanthrene-treated DBA/2 mice or guinea pigs. The two complementary radioimmunoassay methods are sensitive, efficient, and easily applicable for screening large number of tissue samples for MAb-defined cytochrome P-450 phenotype. 相似文献
69.
Fluorescence quenching of human orosomucoid. Accessibility to drugs and small quenching agents.
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The fluorescence behaviour of human orosomucoid was investigated. The intrinsic fluorescence was more accessible to acrylamide than to the slightly larger succinimide, indicating limited accessibility to part of the tryptophan population. Although I- showed almost no quenching, that of Cs+ was enhanced, and suggested a region of negative charge proximal to an emitting tryptophan residue. Removal of more than 90% of sialic acid from the glycan chains led to no change in the Cs+, I-, succinimide or acrylamide quenching, indicating that the negatively charged region originates with the protein core. Quenching as a function of pH and temperature supported this view. The binding of chlorpromazine monitored by fluorescence quenching, in the presence and in the absence of the small quenching probes (above), led to a model of its binding domain on orosomucoid that includes two tryptophan residues relatively shielded from the bulk solvent, with the third tryptophan residue being on the periphery of the domain, or affected allotopically and near the negatively charged field. 相似文献
70.
Philip Skehan Susan J. Friedman 《In vitro cellular & developmental biology. Plant》1985,21(5):288-290
Summary A rapid method has been developed for measuring the cellular protein content of mono- and multilayered anchorage cultures.
Fixed or air dried cultures are stained for 30 min with 0.2% Naphthol Yellow S (NYS) dissolved in 1% acetic acid. Unbound
dye is removed by a series of four 2.5 min washes in 1% acetic acid, and protein-bound dye extracted with 10 mM unbuffered Tris base for spectrophotometric optical density determination at 433 nm. The NYS method exhibited a least-squares
correlation coefficient of 0.99997 with the Oyama-Eagle Lowry method. 相似文献