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101.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
102.
103.
A canine model of hemophilic (factor VIII:C deficiency) bleeding 总被引:8,自引:4,他引:8
A model of bleeding due to clotting factor deficiency has been developed in dogs. Normal and hemophilic (factor VIII:C deficient) animals were used. Bleeding was induced in lightly anesthetized animals by severing the apex of the nail cuticle using a guillotine device. In normal animals, bleeding usually ceased spontaneously after 2-8 min. In contrast, in hemophilic animals, bleeding continued for up to 20 min and necessitated either cauterization or the application of topical thrombin to achieve hemostasis. Pretreatment of the hemophilic animals with canine cryoprecipitate corrected the cuticle bleeding time to within the range noted for normal animals. The method is simple and reproducible and has the advantage that a number of observations can be made sequentially on the same animal. Rebleeding of the cauterized cuticle of the hemophilic animals did not usually occur. This model has considerable potential for the preclinical testing of products considered to bypass or replace factor VIII:C in patients with acquired inhibitors of factor VIII:C and may be adapted to the study of other mechanisms involved in normal and abnormal hemostasis. 相似文献
104.
105.
AR Jones BSC AJP Sandison FRCS WJ Owen MS FRCS 《International journal of clinical practice》1997,51(5):294-295
Pre-clerking of all patients undergoing elective general surgical operations was introduced at our hospital in an attempt to reduce an unacceptably high operation cancellation rate. A prospective audit has been performed on the effect of this policy on the cancellation rate. Before the introduction of pre-clerking there was a marked seasonal variation in the number of patients who failed to attend for surgery, which could be explained by absence on holiday. This seasonal variation disappeared after the start of pre-clerking clinics, but there has been no reduction in the number of cancellations for medical reasons. 相似文献
106.
P. Ferrandon B. Barcelo JC Perche and AR Schoffs 《Fundamental & clinical pharmacology》1994,8(5):446-452
Summary— The suggestion that adenosine may have beneficial effects on post reperfusion survival following cardiac ischaemia has led to the search for agents which increase the concentration of this substance in the ischemic region as a possible therapeutic approach to the treatment of angina and myocardial infarction. In the present study, dipyridamole, soluflazine and lidoflazine, known inhibitors of the nucleotide exchange system, have been shown using an HPLC method to prevent the decrease in the concentration od added adenosine outside human red blood cells in vitro. However, the results suggest that this effect was due to inhibition of adenosine deaminase rather than inhibition of nucleotide exchange as had previously been suggested. The selective inhibitor of adenosine deaminase erythro-9-(2 hydroxy-3-nonyl adenosine) exhibited the same profile of activity in the human red blood cell assay. pIC50 values for the four compounds named above were found to be 6.80 ± 0.09, 6.95 ± .03, 6.10 ± 0.14 and 7.39 ± 0.05 vs adenosine disapearance observed in the extracellular incubation medium respectively. Thus, as the disappearance of adenosine outside the cells was not due to its uptake but to its catabolism, this in vitro method does not appear to be predictive for the ability of compounds to act on adenosine uptake into cardiac myocytes. Any antiischemic action of these agents is more readily explained by an inhibition of the catabolism of adenosine and not by the inhibition of its transport across the membrane of cardiac myocytes. 相似文献
107.
108.
H C Cheng W J Armitage M I Yagoubi D L Easty 《The British journal of ophthalmology》1996,80(4):367-372
AIM: To study the influence of cryoprotectant, cooling rate, and warming rate on recovery and viability of keratocytes from corneas for cryolathing. METHODS: Corneas were frozen at -50 degrees C for 2 minutes either after exposure to 10% dimethyl sulphoxide in Eagle's MEM for 15 minutes at room temperature (about 22 degrees C), or without earlier exposure to the cryoprotectant. Corneas were cooled either rapidly (20 degrees C/min) or slowly (1 degree C/min), and they were warmed either rapidly (> 50 degrees C/min) by direct transfer into medium at 22 degrees C or slowly (< 20 degrees C/min) in air at 22 degrees C. The cryoprotectant was removed by dilution in medium containing 0.5 mol/l sucrose. Recovery of keratocytes was determined by using collagenase digestion to release the cells from the stroma and trypan blue staining. Viability was assessed by the outgrowth of cells from stromal explants in primary tissue culture. RESULTS: The use of a cryoprotectant before freezing was beneficial, irrespective of the different cooling and warming regimens. Both collagenase digestion and tissue culture revealed that keratocyte survival was improved when corneas were warmed rapidly rather than slowly. The collagenase digestion assay showed an apparently higher recovery of keratocytes after slow cooling (54.3%) than after rapid cooling (34.1%), but no differences in cell viability could be demonstrated by primary tissue culture. CONCLUSION: Although in these experiments slow cooling apparently provided the best recovery of keratocyte numbers (though not viability), previous work had revealed some disruption of the epithelial basement membrane after slow cooling. If viable keratocytes and good preservation of epithelial basement membrane are considered to be prerequisites for epikeratophakia lenticules then it is suggested that corneas should be prepared for cryolathing by freezing rapidly after exposure to 10% dimethyl sulphoxide and, following cryolathing, they should be warmed rapidly. 相似文献
109.
Cerebral microgyria, thalamic cell size and auditory temporal processing in male and female rats 总被引:4,自引:2,他引:2
Herman AE; Galaburda AM; Fitch RH; Carter AR; Rosen GD 《Cerebral cortex (New York, N.Y. : 1991)》1997,7(5):453-464
Induction of microgyria by freezing injury to the developing somatosensory
cortex of neonatal rats causes a defect in fast auditory processing in
males, but not in females. It was speculated that early damage to the
cortex has sexually dimorphic cascading effects on other brain regions
mediating auditory processing, which can lead to the observed behavioral
deficits. In the current series of experiments, bilateral microgyri were
induced by placement of a freezing probe on the skulls of newborn male and
female rats, and these animals were tested in adulthood for auditory
temporal processing. Control animals received sham surgery. The brains from
these animals were embedded in celloidin, cut in the coronal plane and the
following morphometric measures assessed: microgyric volume, medial
geniculate nucleus (MGN) volume, cell number, and cell size, and, as a
control, dorsal lateral geniculate nucleus (dLGN) volume, cell number and
cell size. There were no sex differences in the cortical pathology of
lesioned animals. However, microgyric males had more small and fewer large
neurons in the MGN than their sham-operated counterparts, whereas there was
no difference between lesioned and sham-operated females. There was no
effect on dLGN cell size distribution in either sex. Microgyric males were
significantly impaired in fast auditory temporal processing when compared
to control males, whereas lesioned females exhibited no behavioral
deficits. These results suggest that early injury to the cerebral cortex
may have different effects on specific thalamic nuclei in males and
females, with corresponding differences in behavioral effects.
相似文献
110.
MUSTAFA B HOSCAN ALIM KOAR ÜMT GÜMÜTA MEHMET GÜNEY 《International journal of urology》2006,13(3):301-302
Spontaneous migration of an intrauterine device into the bladder is very rare. A 29-year-old woman in whom an intrauterine device had been placed 6 years previously, presented complaining of chronic pelvic pain and recurrent irritative urinary tract symptoms. One year after insertion she had became pregnant and given birth without complications. Intravesical migration of the intrauterine device was confirmed by sonography and cystoscopy. The intrauterine device was removed by suprapubic cystostomy. 相似文献