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1.
Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139-169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme. 相似文献
2.
OBJECTIVES--(a) To compare current vocational training in general practice with that ascertained by a survey in 1980; (b) to compare the training of trainees in formal training schemes with that of trainees arranging their own hospital and general practice posts. DESIGN--National questionnaire survey of United Kingdom and armed services trainees who were in a training practice on 1 April 1989. Questionnaires were distributed by course organisers. SETTING--Research project set up after an ad hoc meeting of trainees at the 1988 national trainee conference. SUBJECTS--2132 Of the 2281 trainees (93%) known to be in a training practice on 1 April 1989. RESULTS--1657 Trainees returned the questionnaires, representing 73% of all trainees known to be in a training practice on 1 April 1989. Between 1980 and 1989 there were significant improvements in the trainee year, and there was also evidence of improvements in general practice study release courses. There was no evidence of improvement in other aspects of training. General practice trainees spent an average of three years in junior hospital posts, which provided very little opportunity for study related to general practice. Training received during tenure of hospital posts differed significantly between trainees in formal schemes and those arranging their own hospital posts. During the trainee year training was almost the same for those in formal schemes and those arranging their own posts. Regions varied significantly in virtually all aspects of general practice training. CONCLUSIONS--The trainee year could be improved further by enforcing the guidelines of the Joint Committee on Postgraduate Training for General Practice. The poor training in junior hospital posts reflected the low priority that training is generally given during tenure of these posts. A higher proportion of general practice trainees should be attached to vocational training schemes. More hospital trainees could attend general practice study release courses if these were designed specifically with the needs of hospital doctors in mind. 相似文献
3.
Potency of L-364,718 as an antagonist of the behavioral effects of peripherally administered cholecystokinin 总被引:2,自引:0,他引:2
A new antagonist of the peripheral cholecystokinin receptor, L-364,718, was found to block the reductions in food intake and exploratory activity induced by intraperitoneal administration of cholecystokinin octapeptide sulfate. L-364,718 significantly reversed the cholecystokinin-induced reduction in feeding at doses of 10 micrograms/kg - 10 mg/kg i.p. L-364,718 significantly reversed the cholecystokinin-induced reduction in exploratory activity at doses of 500 ng/kg - 10 mg/kg i.p. The time course of antagonist activity of L-364,718 was immediate to 90 minutes after intraperitoneal administration. L-364,718 had no significant effect on food intake or exploratory activity when administered alone, over the dose range of 100 ng/kg-10 mg/kg i.p. This compound appears to be at least one hundred times more potent than proglumide or benzotript as an antagonist of the behavioral effects of peripherally administered cholecystokinin. 相似文献
4.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
相似文献
5.
R. Michael Snider Dennis A. Pereira Kelly P. Longo Ralph E. Davidson Frederic J. Vinick Kirsti Laitinen Ece Genc-Sehitoglu Jacqueline N. Crawley 《Bioorganic & medicinal chemistry letters》1992,2(12):1535-1540
UK-73,093 was identified in a screening program as a compound able to displace [3H]-neurotensin from its bovine brain receptor. We describe the discovery of this compound, species differences in receptor affinity and its characterization as a functional neurotensin antogonist in vitro and in vivo. 相似文献
6.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4 下载免费PDF全文
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
7.
M. C. Crawley 《Journal of Zoology》1970,160(1):71-89
The population dynamics of Clethrionomys glareolus Schr.and Apodemus sylvaticus (L.) in mixed woodland in County Durham, were studied from March 1963 to January 1965. Two areas of 0.9 ha (2.25 acres) each were trapped monthly and information was obtained on population size, reproduction, survival and growth from marked animals.
Clethrionomys populations increased from June to an autumn peak; then declined, at first rapidly, but then more slowly in winter, before reaching a spring trough. The breeding season of Clethrionomys was from May to December; juveniles were caught from mid-June to December. Survival was in general poor during the breeding season but good at other times. Survival of young born early in the summer was particularly good on one of the areas and some individuals lived long enough to breed in two successive years. On both areas young born early in the year matured rapidly and bred in the year of their birth. Young born in late summer and early autumn ceased growing at a weight of about 14.5 g, remained immature, and formed the bulk of the overwintering population. Growth was completed at the time of sexual maturation the following spring.
Trapping failed to provide adequate samples of juvenile Apodemus in summer to account for subsequent recruitment. The possibility that a substantial proportion of the adult population of this species was also either trap shy or had emigrated temporarily is discussed. Breeding occurred from April until the following January, but the numbers trapped remained very low throughout the early months of the breeding season. Large scale recruitment of young fecund animals into the trap-revealed population occurred during the autumn. Apodemus males continued to grow rapidly during the winter. 相似文献
Clethrionomys populations increased from June to an autumn peak; then declined, at first rapidly, but then more slowly in winter, before reaching a spring trough. The breeding season of Clethrionomys was from May to December; juveniles were caught from mid-June to December. Survival was in general poor during the breeding season but good at other times. Survival of young born early in the summer was particularly good on one of the areas and some individuals lived long enough to breed in two successive years. On both areas young born early in the year matured rapidly and bred in the year of their birth. Young born in late summer and early autumn ceased growing at a weight of about 14.5 g, remained immature, and formed the bulk of the overwintering population. Growth was completed at the time of sexual maturation the following spring.
Trapping failed to provide adequate samples of juvenile Apodemus in summer to account for subsequent recruitment. The possibility that a substantial proportion of the adult population of this species was also either trap shy or had emigrated temporarily is discussed. Breeding occurred from April until the following January, but the numbers trapped remained very low throughout the early months of the breeding season. Large scale recruitment of young fecund animals into the trap-revealed population occurred during the autumn. Apodemus males continued to grow rapidly during the winter. 相似文献
8.
Pathogenesis of Lethal Shock After Intravenous Staphylococcal Enterotoxin B in Monkeys 总被引:8,自引:1,他引:7
The pathogenesis of shock in the rhesus monkey given intravenous staphylococcal enterotoxin B (SEB) is not understood. Several cardiovascular changes produced by a highly purified preparation of SEB were studied after administration of doses ranging from 50 to 1,000 mug/kg. Irreversible arterial hypotension was found consistently at the higher doses. Arterial blood pressure and cardiac output declined substantially as shock developed. Total peripheral vascular resistance did not rise at any time, but showed a significant fall during the late stages of shock. Portal and central venous pressures remained essentially unchanged. Venous O(2) content and pO(2) declined gradually throughout the period of toxemia, but arterial O(2) content remained constant until just prior to death, when a slight fall was noted in some monkeys. These changes were consistent with a pooling of blood in the peripheral vascular beds and seemed to resemble cardiovascular responses reported to occur in monkeys during shock due to bacterial endotoxin. Epinephrine, administered in the late stages of shock, caused arterial pressure to increase almost immediately and cardiac output to return to normal about 1 min later. Although life could occasionally be prolonged for several hours by continuous or intermittent epinephrine infusions, this therapy never succeeded in reversing the lethal effects of high doses of SEB. 相似文献
9.
Virgil S. Crawley 《The Western journal of medicine》1966,104(1):71-72
10.
Ig VH gene family repertoire of plasma cells derived from lupus-prone MRL/lpr and MRL/++ mice 总被引:1,自引:0,他引:1
J L Komisar K Y Leung R R Crawley N Talal J M Teale 《Journal of immunology (Baltimore, Md. : 1950)》1989,143(1):340-347
VH gene family usage was determined in both spontaneous, in vivo activated plasma cells and LPS-induced plasma cells from individual MRL/lpr mice by using in situ hybridization. It was found that VH gene family expression in spontaneous plasma cells varied from mouse to mouse. Some mice expressed VH families in an apparently random manner similar to that obtained with polyclonal activation. Other mice showed an exaggerated expression of particular VH gene families. VH J558 was overrepresented most frequently, but overrepresentation of VH 7183, Q52, and 36-60 was also observed. Importantly, LPS-induced VH gene family expression in these same mice displaying biased VH family usage in spontaneous plasma cells, appeared normal with no evidence for similar biases in the LPS-induced repertoire. Anti-DNA antibody concentrations and the degree of glomerulonephritis were determined for each mouse to measure the severity of disease. The level of expression of the J558 family was positively correlated with disease severity. The results suggest that the initial autoantibody response is highly diverse but becomes more restricted as the disease progresses. 相似文献