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31.
Gordon M. Wahler Dennis E. Coyle Nicholas Sperelakis 《Molecular and cellular biochemistry》1990,93(1):69-76
Platelet-activating factor (PAF) has been implicated as one of the mediators of cardiac anaphylaxis. This phospholipid has been shown to have numerous effects on a variety of tissues, including the heart. Among these effects are alterations in the resting potential and generation of arrhythmias at very low concentrations. This suggests that PAF may modulate the activity of the background, inwardly-rectifying potassium current (IK1). Thus, the effects of PAF on IK1 were examined at the single channel level. Ventricular cells were isolated from adult guinea pig hearts and single channel currents recorded from cell-attached patches. PAF had substantial effects on the single channel currents at sub-nanomolar concentrations (10–11 to 10–10 M). PAF initially caused flickering of the channels, followed by a gradual prolonged depression of channel activity. Since these potassium channels play a major role in determining the resting potential and excitability of the cardiac cell, the effects of PAF on IK1 may play a major role in the deleterious electrophysiological actions of PAF on the heart.Abbreviations IK1
Inwardly-rectifying background potassium current
- Lyso-PAF
Lyso-platelet-activating factor
- PAF
Platelet-activating factor 相似文献
32.
Nicholas Sperelakis 《Molecular and cellular biochemistry》1990,99(2):97-109
The voltage-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). The slow Ca2+ channels of the heart are regulated by cAMP in a stimulatory fashion. Elevation of cAMP produces a very rapid increase in number of slow channels available for voltage activation during excitation. The probability of a slow channel opening and the mean open time of the channel are increased. Therefore, any agent that increases the cAMP level of the myocardial cell will tend to potentiate Isi, Ca2+ influx, and contraction. The myocardial slow Ca2+ channels are also regulated by cGMP, in a manner that is opposite to that of CAMP. The effect of cGMP is presumably mediated by means of phosphorylation of a protein, as for example, a regulatory protein (inhibitory-type) associated with the slow channel. Preliminary data suggest that calmodulin also may play a role in regulation of the myocardial slow Ca2+ channels, possibly mediated by the Ca2+-calmodulin-protein kinase and phosphorylation of some regulatory-type of protein. Thus, it appears that the slow Ca2+ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of extrinsic and intrinsic factors.VSM cells contain two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Although regulation of voltage-dependent Ca2+ slow channels of VSM cells have not been fully clarified yet, we have made some progress towards answering this question. Slow (L-type, high-threshold) Ca2+ channels may be modified by phosphorylation of the channel protein or an associated regulatory protein. In contrast to cardiac muscle where cAMP and cGMP have antagonistic effects on Ca2+ slow channel activity, in VSM, cAMP and cGMP have similar effects, namely inhibition of the Ca2+ slow channels. Thus, any agent that elevates cAMP or cGMP will inhibit Ca2+ influx, and thereby act to produce vasodilation. The Ca2+ slow channels require ATP for activity, with a K0.5 of about 0.3 mM. C-kinase may stimulate the Ca2+ slow channels by phosphorylation. G-protein may have a direct action on the Ca2+ channels, and may mediate the effects of activation of some receptors. These mechanisms of Ca2+ channel regulation may be invoked during exposure to agonists or drugs, which change second messenger levels, thereby controlling vascular tone. 相似文献
33.
We report the first study of the effect of NaCl on the double-bond isomeric composition of fatty acids and theirsn-1/sn-2 positional distribution in the membrane phospholipids of a moderately halophilic eubacterium. The major phospholipids, phosphatidylethanolamine and phosphatidylglycerol, ofVibrio costicola grown in 1M or 3M NaCl both have ansn-1 saturated,sn-2 unsaturated distribution of fatty acids. There is a greater effect of salinity on the fatty acid composition of phosphatidylglycerol compared with phosphatidylethanolamine. The fatty acids in phosphatidylethanolamine of cultures grown in 1M compared with 3M NaCl have the same unsaturation index and average chain length, but different double-bond isomeric compositions. In comparison, the fatty acid composition of phosphatidylglycerol is more unsaturated, with a different double-bond isomeric distribution, and has a shorter average chain length in cultures grown in 3M compared with 1M NaCl. The pattern of fatty acid isomers of 16:1 and 18:1 shows thatV. costicola uses the anaerobic pathway of fatty acid biosynthesis. The presence of the isomers 16:1c11 and 18:1c13 in the phospholipids of cultures grown in 3M but not in 1M NaCl indicates that external salinity affects the specificity of fatty acid synthetase in this moderately halophilic bacterium. 相似文献
34.
Acetylation at the -amino terminal is a common post-translational modification of many peptides and proteins. In the case of the potent opiate peptide -endorphin, -N-acetylation is a known physiological modification that abolishes opiate activity. Since there are no known receptors for -N-acetyl--endorphin, we have studied the association of this peptide with calmodulin, a calcium-dependent protein that binds a variety of peptides, phenothiazines, and enzymes, as a model system for studying acetylated endorphin-protein interactions. Association of the acetylated peptide with calmodulin was demonstrated by cross-linking with bis(sulfosuccinimidyl)suberate; like -endorphin, adducts containing 1 mol and 2 mol of acetylated peptide per mole calmodulin were formed. Some of the bound peptides are evidently in relatively close proximity to each other since, in the presence of amidated (i.e., lysine-blocked) calmodulin, cross-linking yielded peptide dimers. The acetylated peptide exhibited no appreciable helicity in aqueous solution, but in trifluoroethanol (TFE) considerable helicity was formed. Also, a mixture of acetylated peptide and calmodulin was characterized by a circular dichroic spectrum indicative of induced helicity. Empirical prediction rules, applied earlier to -endorphin, suggest that residues 14–24 exhibit -helix potential. This segment has the potential of forming an amphipathic helix; this structural unit is believed to be important in calmodulin binding. The acetylated peptide was capable of inhibiting the calmodulin-mediated stimulation of cyclic nucleotide phosphodiesterase (EC 3.1.4.17) activity with an effective dose for 50% inhibition of about 3 µM; this inhibitory effect was demonstrated using both an enzyme-enriched preparation as well as highly purified enzyme. Thus, acetylation at the -amino terminal of -endorphin, although abolishing opiate activity, does not interfere with the binding to calmodulin. Indeed, -endorphin and the -N-acetylated peptide behave very similarly with respect to calmodulin association.Portions of this work are in partial fulfillment of the requirements for the Ph.D. degree from Vanderbilt University. 相似文献
35.
A range of surfactants, including the anionic sodium dodecyl sulfate, the cationic cetyltrimethylammonium bromide and the nonionics octylphenoxy polyethoxyethanol (Triton X100) and polyoxyethylene 20 sorbitan monoleate (Tween 80) was studied for effects on proliferation, contractibility and attachment of cultured human fibroblasts. Only ionic surfactants exhibited a stimulatory effect on fibroblast proliferation, whereas all the surfactants tested increased the contraction of collagen gels containing fibroblasts, with the greatest effect from the non-ionic surfactants. This activity was not correlated with an increase of cell population or cell attachment within the collagenous matrix. The activity of the surfactants was seen only at levels close to their LD50 values and in a narrow range of concentrations. Thus, we consider that they are the result of the so-called hormesis phenomenon.Abbreviations CTAB
cetyltrimethyl-ammonium bromide
- FCS
fetal calf serum
- LD100
dose lethal to 100% of exposed
- MCD
maximal contraction dose
- PDL
population doubling level
- SDS
sodium dodecyl sulfate 相似文献
36.
37.
38.
Nicholas F. Hughes 《Environmental Biology of Fishes》1992,33(3):299-305
Synopsis Length-frequency data suggest Nile perch, Lates niloticus, from the Nyanza Gulf grew to a total length of 9 cm by age 118 days and 23 cm by age 287 days. A modified von Bertalanffy growth curve t = 1.35·L(1-e–K(t-t
o)) with the parameters L = 93.1, K = 0.272 and to = 0.046, is suggested to describe growth up to 5 years of age and the relationship t = 1.35·(31.96 + 7.681t) for fish aged 6 years and above. Length-weight relationships were = 0.0234·-gt2.74 for fish between 7 and 15.9 cm total length, = 0.0151·2.94 for fish between 16 and 45.9 cm total length, and = 0.0023·3.44 for fish between 46 and 120 cm total length. Male Nile perch first matured between 50 and 55 cm total length when they were probably 2 years old; female Nile perch first matured between 80 and 85 cm total length when they were probably 4 years old. Small males were common, large males were rare, with the reverse holding for females. Sex change, from male to female, is a possible explanation for this size dimorphism. 相似文献
39.
40.
The relative contributions made by the l-arginine/agmatine/N-carbamoylputrescine/putrescine and the l-ornithine/putrescine pathways to hyoscyamine formation have been investigated in a transformed root culture of Datura stramonium. The activity of either arginine decarboxylase (EC 4.1.1.19) or ornithine decarboxylase (EC 4.1.1.17) was suppressed in vivo by using the specific irreversible inhibitors of these activities, dl--difluoromethylarginine or dl--difluoromethylornithine, respectively. It was found that suppression of arginine decarboxylase resulted in a severe decrease in free and conjugated putrescine and in the putrescine-derived intermediates of hyoscyamine biosynthesis. In contrast, the suppression of ornithine decarboxylase activity stimulated an elevation of arginine decarboxylase and minimal loss of metabolites from the amine and alkaloid pools. The stimulation of arginine decarboxylase was not, however, sufficient to maintain the same potential rate of putrescine biosynthesis as in control tissue. It is concluded that (i) in Datura the two routes by which putrescine may be formed do not act in isolation from one another, (ii) arginine decarboxylase is the more important activity for hyoscyamine formation, and (iii) the formation of polyamines is favoured over the biosynthesis of tropane alkaloids. An interaction between putrescine metabolism and other amines is also indicated from a stimulation of tyramine accumulation seen at high levels of dl--difluoromethylornithine.Abbreviations ADC
arginine decarboxylase
- DFMA
dl--dif-luoromethylarginine
- DFMO
dl--difluoromethylornithine
- MPO
N-methylputrescine oxidase
- ODC
ornithine decarboxylase
- PMT
putrescine N-methyltransferase
We are indebted to Dr. E.W.H. Bohme of Merrell Dow Research Laboratories (Cincinnati, Ohio, USA) for kind gifts of DFMO and DFMA and to Dr. M.J.C. Rhodes for helpful advice and discussion. 相似文献