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1.
用体外培养的人的伪表皮作为模型,进行药物毒理学作用的研究,观察了二甲亚砜(DMSO)在不同浓度和不同接触时间条件下,对人的伪表皮细胞脱氧核糖核酸(DNA)、核糖核酸(RNA)和蛋白质合成的影响:随着接触时间的延长,DNA、RNA和蛋白质合成均受抑制。低浓度条件下(1%),DNA、RNA和蛋白质合成增加;在15~50%浓度下,DNA和蛋白质合成抑制,而RNA合成仍增加;在高浓度条件下(70%~100%),DNA、RNA和蛋白质合成均明显抑制。 相似文献
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The aetiology, morphology and clinical significance of Brunn's nests in human bladder urothelium are poorly understood. In the present study, 9% of a population of 100 consenting patients undergoing diagnostic or review cystoscopies were histologically found to have Brunn's nests, although their presence was not detected endoscopically. Of the nine cases, four were diagnosed with cystitis cystica, two with bladder papillomata, one with transitional cell carcinoma and cystitis cystica, and two were considered to be macroscopically normal. Mucosal biopsies were removed from areas unaffected by macroscopic abnormalities. Brunn's nests consisted of rounded collections of cells, whose nuclei contained prominent nucleoli and occasional nuclear bodies. The cytoplasm frequently contained clusters of mitochondria, together with Golgi membranes and cisternae of granular endoplasmic reticulum while small membrane bound vesicles containing electron dense material were present in some cells. Presumptive lysosomes were rarely observed. Thus Brunn's nest cells generally resembled normal urothelial cells in both their nuclear and cytoplasmic fine structure. Brunn's nests were surrounded by a basal lamina and loose connective tissue containing fenestrated capillaries. 相似文献
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Lestou VS O'Connell JX Ludkovski O Gosling H Lesack D Horsman DE 《Cancer Genetics and Cytogenetics》2002,139(1):44-47
An 80-year-old male presented with a lobulated mass in the lower abdominal wall. A diagnosis of an intermediate grade myofibroblastic spindle cell sarcoma was made. Cytogenetic analysis demonstrated a complex karyotype with a der(6), a small marker and five, different in size, ring chromosomes. Fluorescence in situ hybridization (FISH), multiplex FISH, and multicolor banding analysis was used to further delineate this complex karyotype. The der(6) was shown to be a der(18)t(6;18;9;12;18), the marker chromosome was identified as del(17), and the ring chromosomes as r(9) and r(12;18)x4. Amplification of 18 and coamplification of 12p and 12q was detected in the ring and marker chromosomes. No intercellular heterogeneity was observed although a few micronuclei containing chromosome 18 and anaphase bridges, containing chromosome 12 material, the result of bridge-fusion-bridge (BFB) cycles, were observed. Our findings combined with results from others indicate that amplification of chromosomes 12 and 18 as well as BFB phenomena characterize this type of sarcoma. 相似文献
7.
Telfer JF; Thomson AJ; Cameron IT; Greer IA; Norman JE 《Human reproduction (Oxford, England)》1997,12(10):2306-2312
Superoxide, an agent which attenuates the half-life of nitric oxide, is
metabolized and synthesized by superoxide dismutase (SOD) and xanthine
oxidase, respectively. Over the last few years much work has focused on the
role of nitric oxide in human parturition. The aim of this study was to
determine whether the onset of human parturition is associated with a
change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD),
manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the
uterus. Samples of myometrium, placenta, decidua and fetal membranes were
obtained from women before and after the onset of labour at term.
Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine
oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like
immunoreactivity was detected in syncytiotrophoblast cells, villous stromal
cells and endothelial cells of blood vessels in the placenta. In the
myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial
cells and to some vascular smooth muscle cells. In the fetal membranes we
observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion,
extravillous trophoblast and decidua. There was no difference in SOD enzyme
activity or staining intensity for SOD between different cell types before
and during labour. Xanthine oxidase immunoreactivity was identified in each
of the tissues examined and again there was no difference in immunostaining
in tissues obtained from women delivered before or after the onset of
labour. These results show that the pregnant uterus is capable of both
synthesizing and degrading superoxide and suggest that superoxide dismutase
and xanthine oxidase may play a role in the maintenance of uterine
quiescence during pregnancy, but not in the initiation of parturition.
相似文献
8.
Pre-eclampsia, one of the most significant health problems inhuman pregnancy, complicates 6-7% of all gestations and is theleading cause of fetal growth retardation, infant morbidityand mortality, premature birth and maternal death. Recent researchimplicates free radicals in the pathophysiology of pre-eclampsia.This review covers the biochemistry of nitric oxide (NO) andpossible interactions with other free radicals. Studies in therat show that pregnancy is associated with enhanced productionand responsiveness to NO in both reproductive tissues and bloodvessels. Rats infused with NG-nitro-L-arginine methyl ester(L-NAME, a NO synthase inhibitor) have been used as an animalmodel of pre-eclampsia, and the effects of steroid hormoneson blood pressure in this model have been tested. Results suggestthat pre-eclampsia may be a state of NO deficiency. However,in humans there seem to be contradictions regarding the involvementof NO in maternal adaptation to pregnancy. It is suggested thatNO may be one of several systems that act in concert to maintaina symbiotic relationship between mother and fetus. However,the input of each system may be genetically determined. 相似文献
9.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
10.
Shamsah Kazani David J. Rowlands Ivan Bottoli Julie Milojevic Jose Alcantara Ieuan Jones Kenneth Kulmatycki Surendra Machineni Lidia Mostovy Ian Nicholls Jerry A. Nick Steven M. Rowe Nicholas J. Simmonds Raju Vegesna Jeroen Verheijen Henry Danahay Martin Gosling Phaninatha Sarma Ayalavajjala Robert Strieter 《Journal of cystic fibrosis》2021,20(2):250-256
BackgroundThis is the first-in-human study of icenticaftor, an oral potentiator of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) channel. Restoration of CFTR activity has shown significant clinical benefits, but more studies are needed to address all CFTR mutations.MethodsSafety, pharmacodynamics/pharmacokinetics of icenticaftor were evaluated in a randomized, double-blind, placebo-controlled study in healthy volunteers. Efficacy was assessed in adult CF patients with ≥1 pre-specified CFTR Class III or IV mutation (150 and 450 mg bid), or homozygous for F508del mutation (450 mg bid). Primary efficacy endpoint was change from baseline in lung clearance index (LCI2.5). Secondary endpoints included %predicted FEV1 and sweat chloride level.ResultsClass IV mutations were present in 22 patients, Class III in 2 (both S549N), and 25 were homozygous for F508del. Icenticaftor was well-tolerated in healthy and CF subjects with no unexpected events or discontinuations in the CF groups. The most frequent study-drug related adverse events in CF patients were nausea (12.2%), headache (10.2%), and fatigue (6.1%). Icenticaftor 450 mg bid for 14 days showed significant improvements in all endpoints versus placebo in patients with Class III and IV mutations; mean %predicted FEV1 increased by 6.46%, LCI2.5 decreased by 1.13 points and sweat chloride decreased by 8.36 mmol/L. No significant efficacy was observed in patients homozygous for a single F508del.ConclusionsIcenticaftor was safe and well-tolerated in healthy volunteers and CF patients, and demonstrated clinically meaningful changes in lung function and sweat chloride level in CF patients with Class III and IV CFTR mutations.ClinicalTrials.gov: NCT02190604 相似文献