全文获取类型
收费全文 | 1622篇 |
免费 | 196篇 |
国内免费 | 29篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 146篇 |
妇产科学 | 24篇 |
基础医学 | 215篇 |
口腔科学 | 91篇 |
临床医学 | 179篇 |
内科学 | 354篇 |
皮肤病学 | 49篇 |
神经病学 | 32篇 |
特种医学 | 177篇 |
外科学 | 238篇 |
综合类 | 40篇 |
预防医学 | 100篇 |
眼科学 | 40篇 |
药学 | 56篇 |
中国医学 | 3篇 |
肿瘤学 | 97篇 |
出版年
2023年 | 14篇 |
2022年 | 11篇 |
2021年 | 16篇 |
2020年 | 14篇 |
2019年 | 9篇 |
2018年 | 47篇 |
2017年 | 46篇 |
2016年 | 43篇 |
2015年 | 63篇 |
2014年 | 78篇 |
2013年 | 110篇 |
2012年 | 51篇 |
2011年 | 34篇 |
2010年 | 80篇 |
2009年 | 92篇 |
2008年 | 33篇 |
2007年 | 53篇 |
2006年 | 48篇 |
2005年 | 29篇 |
2004年 | 34篇 |
2003年 | 17篇 |
2002年 | 21篇 |
2001年 | 24篇 |
2000年 | 13篇 |
1999年 | 25篇 |
1998年 | 101篇 |
1997年 | 87篇 |
1996年 | 99篇 |
1995年 | 64篇 |
1994年 | 75篇 |
1993年 | 40篇 |
1992年 | 27篇 |
1991年 | 28篇 |
1990年 | 23篇 |
1989年 | 34篇 |
1988年 | 33篇 |
1987年 | 31篇 |
1986年 | 27篇 |
1985年 | 31篇 |
1984年 | 14篇 |
1983年 | 9篇 |
1982年 | 22篇 |
1981年 | 15篇 |
1980年 | 16篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1976年 | 13篇 |
1975年 | 10篇 |
1961年 | 3篇 |
排序方式: 共有1847条查询结果,搜索用时 15 毫秒
41.
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
42.
Francesca Oliviero Paola Galozzi Anna Scanu Francesca Galuppini Vanni Lazzarin Silvia Brocco Giampietro Ravagnan Paolo Sfriso Roberta Ramonda Paolo Spinella Leonardo Punzi Gianmaria Pennelli Roberto Luisetto 《Nutrients》2021,13(3)
Background: Polydatin is a stilbenoid with important antioxidant, anti-inflammatory, and immunomodulating properties. The aim of this study was to assess the anti-inflammatory preventive effect of polydatin in the mouse model of acute arthritis induced by calcium pyrophosphate (CPP) crystals. Methods: Acute arthritis was induced by the injection of a suspension of sterile CPP crystals into the ankle joint of Balb/c mice. Animals were randomized to receive polydatin or colchicine (the control drug) according to a prophylactic and a therapeutic protocol. The primary outcome was the variation of ankle swelling obtained after crystal injection and treatment, while histological parameters such as leukocyte infiltration, IL-1ß and CXCL1 levels and tissue expression were considered as secondary outcomes. Results: Prophylactic treatment with PD significantly diminished ankle swelling after 48 h from crystal injection. Secondary outcomes such as leukocyte infiltration, necrosis, edema, and synovitis were also decreased. PD caused a reduction in circulating levels of IL-1ß and CXCL1, as well as their tissue expression. By contrast, the therapeutic administration of PD did not have any beneficial effect. Conclusions: PD can effectively prevent acute inflammatory response to crystals in the mouse model of CPP crystal-induced arthritis. These results suggest that this bioactive compound might be used in the prevention of crystal-induced acute attacks in humans. 相似文献
43.
Maša Davidović Nadine Zielonke Iris Lansdorp-Vogelaar Nereo Segnan Harry J. de Koning Eveline AM. Heijnsdijk 《Value in health》2021,24(3):353-360
ObjectivesTo quantify the impact of mammography-based screening on the quality of life, disability-adjusted life years (DALYs) averted or quality-adjusted life years (QALYs) gained can be used. We aimed to assess whether the use of DALYs averted or QALYs gained will lead to different cost-effective screening strategies.MethodsUsing the microsimulation model MISCAN, we simulated different breast cancer screening strategies varying in starting age (starting at 45, 47, and 50 years), stopping age (stopping at 69, 72, and 74 years), and frequency (annual [A], biennial [B], combination of both [A + B], and triennial [T]). In total, we defined 24 different breast cancer screening strategies, including no screening as a reference strategy. We calculated incremental cost-effectiveness ratios (ICERs) and compared which strategies were on the efficiency frontiers for DALYs and QALYs.ResultsBreast cancer screening averted between 46.00 and 105.58 DALYs and gained between 28.69 and 64.50 QALYs per 1000 women. For DALYs there were 5 strategies on the efficiency frontier (T50-69, T50-74, T45-74, B45-74, and A45-74). The same strategies plus one (B45-72) were on the efficiency frontier for QALYs.ConclusionsUsing DALYs averted instead of QALYs gained to assess the effects on quality of life from breast cancer screening in the Dutch population yields differences in ICERs, but almost the same strategies were on the efficiency frontiers. Whether the choice in outcome measure leads to a difference in optimal policy depends on the cost-effectiveness threshold. 相似文献
44.
SCHOLZ J.; ROEWER N.; RUM U.; SCHMITZ W.; SCHOLZ H.; SCHULTE AM ESCH J. 《British journal of anaesthesia》1991,66(6):692-696
-Adrenoceptor stimulation may induce malignant hyperthermia(MH) in vivo. Consequently, we have investigated the effectsof the -adrenoceptor agonist phenylephrine and, for comparison,the effects of the ß-adrenoceptor agonist isoproterenolon inositol-lipid metabolism of malignant hyperthermia susceptible(MHS) and healthy control (MHN) swine. The experiments wereperformed on electrically stimulated (frequency 0.2 Hz) trabeculaeisolated from the right ventricles of the hearts of MHS andMHN animals. After labelling with [3H] inositol for 6 h, differentinositol phosphates were measured by high pressure liquid chromatography,including inositol 1 - phosphate, inositol 1,4-bisphosphate,inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP3)and inositol 1,3,4,5 - tetrakisphosphate. After stimulationwith isoproterenol, the inositol phosphate content did not increaseor vary between muscle from MHS and MHN animals. In contrast,all inositol phosphates increased after stimulation with phenylephrinein both muscle types, the effects being greater in MHS thanin MHN, especially as regards 1,4,5-IP3 content. As 1,4,5-IP3,a presumed second messenger, has been shown to mobilize intracellularcalcium, it is concluded that an enhanced -adrenergic responseis involved in the development of MH.
*Address for correspondence: Abteilung für Anästhesiologie,Universitäts-Krankenhaus Eppendorf, Martinistrasse52, D-2000Hamburg 20, Germany.
Presented in part at the 1989 Meeting of the European Academyof Anaesthesiology in Bonn. 相似文献
45.
46.
SK Roy AM Tomkins SM Akramuzzaman RH Behrens R Haider D Mahalanabis G Fuchs 《Archives of disease in childhood》1997,77(3):196-200
OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished. 相似文献
47.
This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background. 相似文献
48.
Amicarelli F; Bucciarelli T; Poma A; Aimola P; Di Ilio C; Ragnelli AM; Miranda M 《Carcinogenesis》1998,19(3):519-523
The effects of methylglyoxal on the growth of a line of human melanoma
cells are investigated. Methylglyoxal inhibits cell growth in a dose-
dependent manner and causes an increase in glyceraldehyde 3-phosphate
dehydrogenase, and glyoxalase 1 and glyoxalase 2 specific activities. The
cellular response to increasing concentrations of methylglyoxal in the
culture medium is also studied by measuring L-lactate production,
reduced-oxidized glutathione levels and apoptotic cell death. Methylglyoxal
seems to promote a change of cell population phenotypic repertoire toward a
more monomorphic phenotype. In conclusion, methylglyoxal seems to induce an
enzymatic cellular response that lowers methylglyoxal levels and selects
the most resistant cells.
相似文献
49.
The hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in 6-
thioguanine (TG) resistant T-lymphocytes is a useful target for the study
of somatic in vivo mutagenesis, since it provides information about a broad
spectrum of mutation. Mutations in the hprt coding region were studied in
124 TG-resistant T-cell clones from 38 healthy, non- smoking male donors
from a previously studied population of bus maintenance workers,
fine-mechanics and laboratory personnel. Their mean age was 43 years (range
23-64) and their hprt mutant frequency was 9.3 +/- 5.2 x 10(-6) (mean +/-
SD, range 1.4-22.6 x 10(-6)). Sequence analysis of hprt cDNA identified 115
unique mutations; 76% were simple base substitutions, 10% were +/-1 bp
frameshifts, and 10% were small deletions within exons (3-52 bp). In
addition, two tandem base substitutions and one complex mutation were
observed. Simple base substitutions were observed at 55 (20%) of 281 sites
known to be mutable in the hprt coding sequence. The distribution of these
mutations was significantly different than would be expected based upon a
Poisson distribution (P < 0.0001), suggesting the existence of
'hotspots'. All of the 87 simple base substitutions occurred at known
mutable sites, but eight were substitutions of a kind that have not
previously been reported at these sites. The most frequently mutated sites
were cDNA positions 197 and 146, with six and five independent mutations
respectively. Four mutations were observed at position 131, and three each
at positions 143, 208, 508 and 617. Transitions (52%) were slightly more
frequent than tranversions (48%), and mutations at GC base pairs (56%) more
common than mutations at AT base pairs (44%). GC > AT was the most
common type of base pair substitution (37%). The majority of the mutations
at GC base pairs (78%) occurred at sites with G in the non-transcribed
strand. All but one of eight mutations at CpG- sites were of the kind
expected from deamination of methylated cytosine. Deletion of a single base
pair (-1 frameshift) was three times more frequent than insertion of a
single bp (+1 frameshift). Almost half (6/13) of the small (3-52 bp)
deletions within the coding sequence clustered in the 5' end of exon 2.
Short repeats and other sequence motifs that have been associated with
replication error were found in the flanking regions of most of the
frameshifts and small deletions. However, several differences in the local
sequence context between +/-1 frameshift and deletion mutations were also
noticed. The present results identify positions 197, 146 and possibly 131
as hotspots for base substitution mutations, and confirm previously
reported hotspots at positions 197, 508 and 617. In addition, the earlier
notion of a deletion hotspot in the 5'end of exon 2 was confirmed. The
observations of these mutational cluster regions in different human
populations suggest that they are due to endogeneous mechanisms of
mutagenesis, or to ubiquitous environmental influences. The emerging
background spectrum of somatic in vivo mutation in the human hprt gene
provides a useful basis for comparisons with radiation or chemically
induced mutational spectra, as well as with gene mutations in human tumors.
相似文献
50.