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51.
Correlation of Rates of Calcium Entry and Release of Endogenous Norepinephrine in Rat Brain Region Synaptosomes 总被引:6,自引:6,他引:0
Voltage-dependent 45Ca2+ uptake and endogenous norepinephrine (NE) release were measured simultaneously in synaptosomes isolated from rat hypothalamus, brainstem, and cerebellum at 1, 3, 5, 15, and 30 s. In synaptosomes depolarized by 125 mM KCl, 45Ca2+ uptake and NE release exhibited fast and slow components. Rates of NE release and 45Ca2+ uptake were fastest from 0 to 1 s. NE release and 45Ca2+ uptake rates from 1 to 5 s were less than 15% of 0-1 s rates. Both resting (5 mM KCl) and depolarization-induced (125 mM KCl) NE release paralleled 45Ca2+ uptake from 1 to 30 s. Voltage-dependent NE release was approximately 1% and 2% of total synaptosomal NE content at 1- and 30-s measurement intervals, respectively, and did not differ between the three brain regions studied. Calcium and potassium dependence studies showed that NE release was stimulated by increased potassium and that depolarization-induced NE release was dependent on the presence of external calcium. These results show that calcium-dependent NE release from synaptosomes is correlated with calcium entry. Both processes exhibit fast and slow temporal components. 相似文献
52.
Leslie C. McKinney M. Danko Catherine J. Smith Ted Begenisich 《The Journal of membrane biology》1985,83(1-2):177-186
Summary The permeability of the Na channel of squid giant axon to organic cations and small nonelectrolytes was studied. The compounds tested were guanidinium, formamidinium, and14C-labeled urea, formamide, thiourea, and acetone. Permeability was calculated from measurements of reversal potential and influx on internally perfused, voltage clamped squid axons. The project had two objectives: (1) to determine whether different methods of measuring the permeability of organic cations yield similar values and (2) to see whether neutral analogs of the organic cations can permeate the Na channel. Our results show that the permeability ratio of sodium to a test ion depends upon the ionic composition of the solution used. This finding is consistent with the view put forward previously that the Na channel can contain more than one ion at a time. In addition, we found that the uncharged analogs of permeant cations are not measurably permeant through the Na channel, but instead probably pass through the lipid bilayer. 相似文献
53.
Recessive Mutations from Natural Populations of NEUROSPORA CRASSA That Are Expressed in the Sexual Diplophase 总被引:2,自引:0,他引:2 下载免费PDF全文
Wild-collected isolates of Neurospora crassa Shear and Dodge were systematically examined for recessive mutations affecting the sexual phase of the life cycle, which is essentially diploid. Seventy-four of 99 wild-collected isolates from 26 populations in the United States, India and Pakistan carried one or more recessive mutations that reduced fertility significantly when homozygous; mutations affecting spore morphology were also detected. Limited complementation tests indicate that most of the 106 recovered mutations are unique.--The recessive diplophase (= sexual phase) mutations were uncovered by crossing each wild-collected isolate to a marked two-chromosome double-reciprocal translocation strain as "balancer." Surviving progeny receive approximately 60% of their genome from the wild parent, but receive the mating-type allele from the "balancer" parent. These progeny were backcrossed to the wild parent and were also crossed with a standard laboratory strain (fl). Reduced fertility in the backcross vs. normal fertility in the cross with the laboratory standard signals the presence of a recessive mutation in the wild-collected isolate.--Most of the mutants (95 of 106) fall into two major classes: those producing barren perithecia with no or few viable ascospores (51) and those with spore maturation defects (44). Most of the recessive barrens result either from an early block in meiosis of ascus development (25) or from a late disturbance in postmeiotic ascus behavior (18).--These recessive mutations are formally equivalent to recessive lethals in higher eukaryotes and may be important in determining the breeding structure of natural Neurospora populations. 相似文献
54.
GABAA receptor agonists modulate [3H]diazepam binding in rat cortical membranes with different efficacies. At 23 degrees C, the relative potencies for enhancement of [3H]diazepam binding by agonists parallel their potencies in inhibiting [3H]gamma-aminobutyric acid [( 3H]GABA) binding. The agonist concentrations needed for enhancement of [3H]diazepam binding are up to 35 times higher than for [3H]GABA binding and correspond closely to the concentrations required for displacement of [3H]bicuculline methochloride (BMC) binding. The maximum enhancement of [3H]diazepam varied among agonists: muscimol = GABA greater than isoguvacine greater than 3-aminopropane sulphonic acid (3APS) = imidazoleacetic acid (IAA) greater than 4,5,6,7-tetrahydroisoxazolo (4,5,6)-pyridin-3-ol (THIP) = taurine greater than piperidine 4-sulphonic acid (P4S). At 37 degrees C, the potencies of agonists remained unchanged, but isoguvacine, 3 APS, and THIP acquired efficacies similar to GABA, whereas IAA, taurine, and P4S maintained their partial agonist profiles. At both temperatures the agonist-induced enhancement of [3H]diazepam binding was reversible by bicuculline methobromide and by the steroid GABA antagonist RU 5135. These results stress the importance of studying receptor-receptor interaction under near-physiological conditions and offer an in vitro assay that may predict the agonist status of putative GABA receptor ligands. 相似文献
55.
Timothy J. Lansing Joseph Franker Leslie M. Jenkins 《The Journal of eukaryotic microbiology》1985,32(1):126-139
The misaligned undulating membrane (mum) mutant of Tetrahymena thermophila is a non-conditional, single gene recessive mutation. The major effect of the mum mutation is the production of multiple undulating membrane (UM) fragments in the oral apparatus (OA). The ultrastructure of the UM fragments of mum OAs is identical to that of the single UM of wild-type OAs. Analysis of OA development at midbody using a combination of light microscopy of protargol-stained cells and SEM of demembranated whole cells showed that the phenotypic effect of the mum mutation first becomes evident during mid to late stage 4 and is fully manifested in early stage 5. The effect of the mutation involves a proliferation of excess basal bodies in the UM field. Subsequent events in the development of the mum OA from mid to late stage 5 are identical to those in wild-type OAs. This study suggests that the mum mutation establishes conditions that allow the production of multiple UMs and thus reveals that the UM field is competent for the complete and coordinated development of several adjacent UMs. This level of regional control is not clearly evident when a single UM is present. The comparison of development of wild-type and mum OAs required an extensive reanalysis of stages 4 and 5 of normal oral development. On the basis of current and previous observations, we propose a new and more subdivided staging system for oral development in Tetrahymena. 相似文献
56.
57.
Diffusion coefficient of fluorescein-labeled tubulin in the cytoplasm of embryonic cells of a sea urchin: video image analysis of fluorescence redistribution after photobleaching 总被引:19,自引:12,他引:7 下载免费PDF全文
E D Salmon W M Saxton R J Leslie M L Karow J R McIntosh 《The Journal of cell biology》1984,99(6):2157-2164
The diffusion coefficient of tubulin has been measured in the cytoplasm of eggs and embryos of the sea urchin Lytechinus variegatus. We have used brain tubulin, conjugated to dichlorotriazinyl-aminofluorescein, to inject eggs and embryos. The resulting distributions of fluorescence were perturbed by bleaching with a microbeam of light from the 488-nm line of an argon ion laser. Fluorescence redistribution after photobleaching was monitored with a sensitive video camera and photography of the television-generated image. With standard photometric methods, we have calibrated this recording system and measured the rates of fluorescence redistribution for tubulin, conjugated to dichlorotriazinyl-aminofluorescein, not incorporated into the mitotic spindle. The diffusion coefficient (D) was calculated from these data using Fick's second law of diffusion and a digital method for analysis of the photometric curves. We have tested our method by determining D for bovine serum albumin (BSA) under conditions where the value is already known and by measuring D for fluorescein-labeled BSA in sea urchin eggs with a standard apparatus for monitoring fluorescence redistribution after photobleaching. The values agree to within experimental error. Dcytoplasmtubulin = 5.9 +/- 2.2 X 10(-8) cm2/s; DcytoplasmBSA = 8.6 +/- 2.0 X 10(-8) cm2/s. Because DH2OBSA = 68 X 10(-8) cm2/s, these data suggest that the viscosity of sea urchin cytoplasm for protein is about eight times that of water and that most of the tubulin of the sea urchin cytoplasm exists as a dimer or small oligomer, which is unbound to structures that would impede its diffusion. Values and limitations of our method are discussed, and we draw attention to both the variations in D for single proteins in different cells and the importance of D for the upper limit to the rates of polymerization reactions. 相似文献
58.
Assembly properties of fluorescein-labeled tubulin in vitro before and after fluorescence bleaching 总被引:12,自引:12,他引:0 下载免费PDF全文
R J Leslie W M Saxton T J Mitchison B Neighbors E D Salmon J R McIntosh 《The Journal of cell biology》1984,99(6):2146-2156
Brain tubulin has been conjugated with dichlorotriazinyl- aminofluorescein (DTAF) to form a visualizable complex for the study of tubulin dynamics in living cells. By using several assays we confirm the finding of Keith et al. (Keith, C. H., J. R. Feramisco, and M. Shelanski, 1981, J. Cell Biol., 88:234-240) that DTAF-tubulin polymerizes like control tubulin in vitro. The fluorescein moiety of the complex is readily bleached by the 488-nm line from an argon ion laser. When irradiations are performed over short times (less than 1 s) and in the presence of 2 mM glutathione, a mixture of DTAF-tubulin and control protein (as occurs after microinjection of the fluorescent conjugate into living cells) will retain full polymerization activity. Slow bleaching (approximately 5 min) or bleaching without glutathione promotes formation of covalent cross-links between neighboring polypeptides and kills the polymerization activity of DTAF-tubulin, including some molecules that are neither cross-linked nor bleached. Even under conditions that damage DTAF-tubulin, however, DTAF- microtubules are not destroyed by bleaching. They will continue to elongate by addition of DTAF-tubulin subunits to their free ends, and they neither bind nor exchange subunits along their lateral surfaces. These results suggest that DTAF-tubulin is a suitable analog for tubulin, both in studies of protein incorporation and for investigations of fluorescence redistribution after photobleaching. 相似文献
59.
Structural evidence for ligand-induced sequential conformational changes in glyceraldehyde 3-phosphate dehydrogenase 总被引:2,自引:0,他引:2
Glyceraldehyde 3-phosphate dehydrogenase is a tetramer of four chemically identical subunits which requires the cofactor nicotinamide adenine dinucleotide (NAD) for activity. The structure of the holo-enzyme from Bacillus stearothermophilus has recently been refined using X-ray data to 2.4 A resolution. This has facilitated the structure determination of both the apo-enzyme and the enzyme with one molecule of NAD bound to the tetramer. These structures have been refined at 4 A resolution using the constrained-restrained parameter structure factor least-squares refinement program CORELS. When combined with individual atomic temperature factors from the holo-enzyme, these refined models give crystallographic R factors of 30.2% and 30.4%, respectively, for data to 3 A resolution. The apo-enzyme has 222 molecular symmetry, and the subunit structure is related to that of the holo-enzyme by an approximate rigid-body rotation of the coenzyme binding domain by 4.3 degrees with respect to the catalytic domains, which form the core of the tetramer. The effect of this rotation is to shield the coenzyme and active site from solvent in the holo-enzyme. In addition to the rigid-body rotation, there is a rearrangement of several residues involved in NAD binding. The structure of the 1 NAD enzyme is asymmetric. The subunit which contains the bound NAD adopts a conformation very similar to that of a holo-enzyme subunit, while the other three unliganded subunits are very similar to the apo-enzyme conformation. This result provides unambiguous evidence for ligand-induced sequential conformational changes in B. stearothermophilus glyceraldehyde 3-phosphate dehydrogenase. 相似文献
60.
Comparative aspects of the area postrema: fine-structural considerations help to determine its function 总被引:1,自引:0,他引:1
R. A. Leslie 《Cellular and molecular neurobiology》1986,6(2):95-120
The area postrema is a circumventricular organ of the fourth ventricle of the mammalian brain. Although there are distinct gross anatomical differences in the appearance of this organ between "lower" mammals such as rodents and lagomorphs and "higher" mammals such as carnivores and primates, its fine structure is remarkably similar in all species studied. There are many suggestions in the literature for a specific function for this area of the brain, ranging from its being a chemoreceptive trigger zone for the emetic response to its being a regulatory nucleus for the sleep cycle. The present report describes some comparative studies on the ultrastructure of this organ. This information is discussed in relation to what is known about the neurochemistry of the area postrema and its connections with other brain regions and visceral structures. A suggestion is offered that our current knowledge of the area postrema is consistent with its performing many of its proposed functions in the context of a regulatory ("fine-tuning") center for many autonomic functions. 相似文献