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111.
Characterisation of renal chloride channel, CLCN5, mutations in hypercalciuric nephrolithiasis (kidney stones) disorders 总被引:4,自引:0,他引:4
Lloyd SE; Gunther W; Pearce SH; Thomson A; Bianchi ML; Bosio M; Craig IW; Fisher SE; Scheinman SJ; Wrong O; Jentsch TJ; Thakker RV 《Human molecular genetics》1997,6(8):1233-1239
Mutations of the renal-specific chloride channel (CLCN5) gene, which is
located on chromosome Xp11.22, are associated with hypercalciuric
nephrolithiasis (kidney stones) in the Northern European and Japanese
populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has
approximately 12 transmembrane domains, and heterologous expression of
wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying
chloride currents that were markedly reduced or abolished by these
mutations. In order to assess further the structural and functional
relationships of this recently cloned chloride channel, additional CLCN5
mutations have been identified in five unrelated families with this
disorder. Three of these mutations were missense (G57V, G512R and E527D),
one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In
addition, two of the mutations (30:H insertion and E527D) were demonstrated
to be de novo, and the G57V and E527D mutations were identified in families
of Afro-American and Indian origin, respectively. The G57V and 30:H
insertion mutations represent the first CLCN5 mutations to be identified in
the N-terminus region, and the R648Stop mutation, which has been observed
previously in an unrelated family, suggests that this codon may be
particularly prone to mutations. Heterologous expression of the mutations
resulted in a marked reduction or abolition of the chloride currents,
thereby establishing their functional importance. These results help to
elucidate further the structure-function relationships of this renal
chloride channel.
相似文献
112.
Greater numbers of human spermatozoa associate with endosalpingeal cells derived from the isthmus compared with those from the ampulla 总被引:2,自引:3,他引:2
Baillie HS; Pacey AA; Warren MA; Scudamore IW; Barratt CL 《Human reproduction (Oxford, England)》1997,12(9):1985-1992
A simple co-culture bioassay system was used to investigate whether or not
the anatomical origin affected the ability of epithelial cells from the
human uterine (Fallopian) tube to 'bind' spermatozoa. This study was also
used to identify some of the factors which may be involved in the
regulation of sperm-epithelial interactions in vitro by comparing different
tissue culture models and assessing the effect of oestradiol concentration.
Epithelial explants harvested from different regions of human uterine tubes
were co-incubated with a known concentration of motile donor spermatozoa.
All results were adjusted to reflect a standard sperm concentration of 5 x
10(6)/ml. More spermatozoa associated per field of isthmic compared to
ampullary epithelium [isthmus 9.5 +/- 0.9, ampulla 7.1 +/- 0.7 (mean +/-
SEM); n = 36, P < 0.05, ANOVA] and cells from post-menopausal patients
had an apparently reduced ability to bind spermatozoa [isthmus 5.5 +/- 2.0,
ampulla 4.3 +/- 1.4 (mean +/- SEM); n = 4]. Neither menstrual cycle stage
nor addition of mid-cycle concentrations of 17beta-oestradiol (750 pmol/l)
affected the number of spermatozoa which bound to epithelium from either
tubal region. In addition, the number of spermatozoa which bound per field
of polarized explants was greater (P < 0.05) than that bound to
dissociated primary and passaged epithelial cell monolayers. This report is
the first to provide evidence suggestive of a role for sperm- epithelial
binding in the formation of an isthmic sperm reservoir in the human uterine
tube. Results also indicate that oestrogen is not involved in the
regulation of these interactions, and that cell polarity is an important
factor for such associations in vitro.
相似文献
113.
A Daly A MacDonald A Aukett J Williams A Wolf J Davidson IW Booth 《Archives of disease in childhood》1996,75(1):9-16
There are few data to support the use of follow-on formulas in infants from the age of 6 months. In a prospective trial in a deprived inner city area of Birmingham 100 infants who were already receiving pasteurised cows' milk by 6 months of age were enrolled and randomised either to receive a follow-on formula or to continue on cows' milk from 6 months until 18 months. At 18 months of age the follow-on formula group returned to cows' milk and both groups were followed up until 24 months. Iron status, growth, and nutritional status were analysed at intervals of six months. At enrollment, no differences in haematological status were evident. However, by 12 months of age, 31% of the cows' milk group were anaemic (haemoglobin concentration < 110 g/l) compared with only 3% of those receiving follow-on formulas. At 18 months, 33% of the cows' milk group were anaemic compared with only 2% of the follow-on formula group and by 24 months of age none of the follow-on formula group was anaemic, whereas 26% in the cows' milk group still had a haemoglobin of < 110 g/l. Mean corpuscular volume was significantly smaller and ferritin significantly lower in the cows' milk group at 12, 18, and 24 months. Dietary iron intake was higher in the follow-on formula group at 12 and 18 months but not at 24 months, when both groups were back on cows' milk. Infants and toddlers at high risk of iron deficiency are therefore unlikely to become anaemic if receiving a follow-on formula, although the relative merits of follow-on formula compared with an ordinary infant formula remain uncertain. 相似文献
114.
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117.
N. Kanesa-thasan G. J. Chang B. L. Smoak A. Magill M. J. Burrous C. H. Hoke Jr 《Emerging infectious diseases》1998,4(2):299-303
Nucleotide sequence analysis was performed on 14 dengue virus isolates (13 dengue-2 viruses and 1 dengue-3 virus) recovered from febrile soldiers in Somalia in 1993. The dengue-2 viruses were most closely related to dengue-2 virus recovered in Somalia in 1984. However, differences in nucleotide sequence (0.35% to 1.35%) were evident among the 1993 isolates. These differences were closely associated with the geographic location of the infection as well as with different times of infection at the same location. Genetic difference between strains was not associated with differences in clinical features. Molecular analysis of dengue viruses is a useful adjunct to epidemiologic investigation of their distribution over distance and time. 相似文献
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120.
I W Smoak 《Diabetes research and clinical practice》1992,17(3):161-167
The present study investigated the teratogenicity of the oral hypoglycemic agent, tolbutamide, using an in vitro approach, and evaluated the role of its main metabolic effect, hypoglycemia. Teratogenesis was evaluated by culturing early-somite mouse embryos for 24 h in serum from rats treated with tolbutamide (79-117 micrograms/ml) or normal rat serum supplemented with tolbutamide (110-152 micrograms/ml). Tolbutamide-treated serum was then supplemented with glucose to control for potential effects of hypoglycemia. Mouse embryos demonstrated high malformation rates following exposure to serum from tolbutamide-treated rats (79%) or normal rat serum supplemented with tolbutamide (85%) compared with controls (4%), and defects included cardiac, ocular, neural tube, and somite abnormalities. Overall growth was reduced in treated embryos and yolk sacs, as determined by total protein contents. Embryonic growth and malformation rates were not improved by glucose supplementation of hypoglycemic tolbutamide-treated serum. Thus, tolbutamide produces malformation in mouse embryos in vitro at concentrations comparable to those in human serum, and the effects do not appear to be mediated by hypoglycemia. The potential risk of tolbutamide on the developing embryo must be considered in the therapy of pregnant diabetic patients. 相似文献