全文获取类型
收费全文 | 1073篇 |
免费 | 64篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 34篇 |
妇产科学 | 98篇 |
基础医学 | 89篇 |
口腔科学 | 19篇 |
临床医学 | 95篇 |
内科学 | 193篇 |
皮肤病学 | 12篇 |
神经病学 | 72篇 |
特种医学 | 46篇 |
外科学 | 278篇 |
综合类 | 28篇 |
预防医学 | 74篇 |
眼科学 | 8篇 |
药学 | 59篇 |
中国医学 | 3篇 |
肿瘤学 | 39篇 |
出版年
2023年 | 4篇 |
2022年 | 14篇 |
2021年 | 18篇 |
2020年 | 26篇 |
2019年 | 19篇 |
2018年 | 22篇 |
2017年 | 21篇 |
2016年 | 18篇 |
2015年 | 30篇 |
2014年 | 38篇 |
2013年 | 50篇 |
2012年 | 41篇 |
2011年 | 47篇 |
2010年 | 47篇 |
2009年 | 50篇 |
2008年 | 41篇 |
2007年 | 57篇 |
2006年 | 44篇 |
2005年 | 35篇 |
2004年 | 40篇 |
2003年 | 32篇 |
2002年 | 27篇 |
2001年 | 28篇 |
2000年 | 25篇 |
1999年 | 24篇 |
1998年 | 36篇 |
1997年 | 29篇 |
1996年 | 25篇 |
1995年 | 15篇 |
1994年 | 20篇 |
1993年 | 13篇 |
1992年 | 26篇 |
1991年 | 22篇 |
1990年 | 16篇 |
1989年 | 15篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 18篇 |
1985年 | 9篇 |
1984年 | 10篇 |
1983年 | 5篇 |
1982年 | 12篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1975年 | 4篇 |
1972年 | 4篇 |
1970年 | 5篇 |
1967年 | 3篇 |
排序方式: 共有1154条查询结果,搜索用时 31 毫秒
11.
IMPT1, an imprinted gene similar to polyspecific transporter and multi- drug resistance genes 总被引:5,自引:1,他引:5
Dao D; Frank D; Qian N; O'Keefe D; Vosatka RJ; Walsh CP; Tycko B 《Human molecular genetics》1998,7(4):597-608
Human chromosome 11p15.5 and distal mouse chromosome 7 include a
megabase-scale chromosomal domain with multiple genes subject to parental
imprinting. Here we describe mouse and human versions of a novel imprinted
gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a
predicted multi-membrane-spanning protein similar to bacterial and
eukaryotic polyspecific metabolite transporter and multi- drug resistance
pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues
with metabolite transport functions, including liver, kidney, intestine,
extra-embryonic membranes and placenta, and there is strongly preferential
expression of the maternal allele in various mouse tissues at fetal stages.
In post-natal tissues there is persistent expression, but the allelic bias
attenuates. An allelic expression bias is also observed in human fetal and
post-natal tissues, but there is significant interindividual variation and
rare somatic allele switching. The fact that Impt1 is relatively repressed
on the paternal allele, together with data from other imprinted genes,
allows a statistical conclusion that the primary effect of human chromosome
11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative
repression of genes on the paternal homolog. Dosage regulation of the
metabolite transporter gene(s) by imprinting might regulate placental and
fetal growth.
相似文献
12.
Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system 总被引:8,自引:0,他引:8
Hwu YM; Lee RK; Chen CP; Su JT; Chen YW; Lin SP 《Human reproduction (Oxford, England)》1998,13(7):1916-1921
Recently, in-vitro maturation (IVM) of immature human oocytes recovered
from non-stimulated follicles has been applied in the treatment of
infertility. However, in previous reports, very few embryos cultured in
conventional medium have reached the expanded blastocyst stage following
in-vitro maturation and fertilization (IVM/IVF). The objective of this
study was to investigate whether the developmental competence of human
embryos following IVM/IVF could be enhanced by the use of a human ampullary
cell co-culture system. Immature human oocytes were aspirated from small
follicles at Caesarean section and then cultured in medium containing human
menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes
were randomly cultured either in conventional culture medium alone or in
the co-culture system. Of 48 embryos cultured in conventional medium alone,
all arrested at the 2-16- cell stage on day 3 after insemination. Of 46
embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at
the 2-16-cell stage. Six embryos (13%) developed to the morula stage.
Fourteen embryos (30.4%) developed to expanded blastocysts and two
blastocysts were hatching on day 7 after insemination. We conclude that
co-culture significantly enhances the development of blastocysts in embryos
resulting from IVM/IVF.
相似文献
13.
A genetic linkage map for zebrafish: comparative analysis and localization of genes and expressed sequences
下载免费PDF全文
![点击此处可从《Genome research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Gates MA Kim L Egan ES Cardozo T Sirotkin HI Dougan ST Lashkari D Abagyan R Schier AF Talbot WS 《Genome research》1999,9(4):334-347
Genetic screens in zebrafish (Danio rerio) have isolated mutations in hundreds of genes with essential functions. To facilitate the identification of candidate genes for these mutations, we have genetically mapped 104 genes and expressed sequence tags by scoring single-strand conformational polymorphisms in a panel of haploid siblings. To integrate this map with existing genetic maps, we also scored 275 previously mapped genes, microsatellites, and sequence-tagged sites in the same haploid panel. Systematic phylogenetic analysis defined likely mammalian orthologs of mapped zebrafish genes, and comparison of map positions in zebrafish and mammals identified significant conservation of synteny. This comparative analysis also identified pairs of zebrafish genes that appear to be orthologous to single mammalian genes, suggesting that these genes arose in a genome duplication that occurred in the teleost lineage after the divergence of fish and mammal ancestors. This comparative map analysis will be useful in predicting the locations of zebrafish genes from mammalian gene maps and in understanding the evolution of the vertebrate genome. 相似文献
14.
Characterization of a gene encoding survival motor neuron (SMN)-related protein, a constituent of the spliceosome complex 总被引:2,自引:3,他引:2
Talbot K; Miguel-Aliaga I; Mohaghegh P; Ponting CP; Davies KE 《Human molecular genetics》1998,7(13):2149-2156
Mutations in the gene encoding the Survival Motor Neuron (SMN) protein are
responsible for autosomal recessive proximal spinal muscular atrophy (SMA).
SMN orthologues have been identified in the nematode worm Caenorhabditis
elegans and the yeast Schizosaccharomyces pombe but, to date, no human
paralogues have been described. Here we describe identification and
characterization of an SMN-related protein (SMNrp) gene that encodes a
novel protein of 239 amino acids, which has recently been identified as a
constituent of the spliceosome complex and designated SPF30. Significant
similarity to the SMN protein is apparent only within a central region of
SMNrp that represents a tudor domain. The SMNrp/SPF30 gene has been mapped
to chromosome 10q23. It is differentially expressed, with abundant levels
in skeletal muscle. An exclusively nuclear localization for SMNrp in
cultured cells and muscle sections was revealed using GFP fusion constructs
and thereafter confirmed with a polyclonal antibody raised against SMNrp.
Overexpression of SMNrp as a fusion protein in HeLa cells in culture
induced dose-dependent apoptosis with positive TUNEL staining. In addition
to a possible role for this protein as a pro-apoptotic factor, SMN and its
related protein share significant similarities in sequence and cellular
function.
相似文献
15.
CP Schaecher KA Groesch 《American journal of reproductive immunology (New York, N.Y. : 1989)》2006,55(6):405-405
Background: Control of mRNA stability is an essential regulatory process in eukaryotic gene expression. HuR, a 3'UTR mRNA binding protein, can protect AU-rich mRNA from degradation in response to stresses. PlGF, an angiogenic growth factor, contains two consensus AU-rich sites suggesting that under normal conditions HuR may protect PlGF mRNA from degradation. Trophoblast expression of PlGF is significantly decreased in preeclampsia and by hypoxia in vitro . We hypothesize that decreased levels of cytoplasmic HuR may contribute to decreased PlGF expression in hypoxic and preeclamptic trophoblast.
Methods: Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results: Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions: HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects. 相似文献
Methods: Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results: Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions: HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects. 相似文献
16.
Marjolein P de Vries Lisette van den Bemt Karen Aretz Bart PA Thoonen Jean WM Muris Arnold DM Kester Sonja Cloosterman CP Onno van Schayck 《The British journal of general practice》2007,57(536):184-190
BACKGROUND: The efficacy of bed covers that are impermeable to house dust mites has been disputed. AIM: The aim of the present study was to investigate whether the combination of 'house dust mite impermeable' covers and a self-management plan, based on peak flow values and symptoms, leads to reduced use of inhaled corticosteroids (ICS) than self-management alone. DESIGN OF STUDY: Prospective, randomised, double blind, placebo-controlled trial. SETTING: Primary care in a south-eastern region of the Netherlands. METHOD: Asthma patients aged between 16 and 60 years with a house dust mite allergy requiring ICS were randomised to intervention and placebo groups. They were trained to use a self-management plan based on peak flow and symptoms. After a 3-month training period, the intervention commenced using house dust mite impermeable and placebo bed covers. The follow-up period was 2 years. Primary outcome was the use of ICS; secondary outcomes were peak expiratory flow parameters, asthma control, and symptoms. RESULTS: One hundred and twenty-six patients started the intervention with house dust mite impermeable or placebo bed covers. After 1 and 2 years, significant differences in allergen exposure were found between the intervention and control groups (P<0.001). No significant difference between the intervention and control groups was found in the dose of ICS (P = 0.08), morning peak flow (P = 0.52), peak flow variability (P = 0.36), dyspnoea (P = 0.46), wheezing (P = 0.77), or coughing (P = 0.41). There was no difference in asthma control between the intervention and control groups. CONCLUSION: House dust mite impermeable bed covers combined with self-management do not lead to reduced use of ICS compared with self-management alone. 相似文献
17.
Ferrer I Blanco R Carmona M Ribera R Goutan E Puig B Rey MJ Cardozo A Viñals F Ribalta T 《Brain pathology (Zurich, Switzerland)》2001,11(2):144-158
Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in taupathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double-labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double-labelling immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation-independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation-independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large numbers of tau-positive glial cells in PSP and CBD, as seen with double-labelling immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD. 相似文献
18.
19.
The effectiveness of a treatment protocol for male lower urinary tract symptoms in general practice: a practical randomised controlled trial
下载免费PDF全文
![点击此处可从《The British journal of general practice》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Roelf JC Norg Kees van de Beek Piet JM Portegijs CP Onno van Schayck J Andr Knottnerus 《The British journal of general practice》2006,56(533):938-944
BACKGROUND: Randomised controlled trials have shown the efficacy of several treatment modalities for lower urinary tract symptoms (LUTS) in selected populations. The effectiveness in daily practice has hardly been investigated, especially in primary care and is dependent on choices between all possible treatment options and best investigated in a comprehensive study, including all treatment modalities (watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors, and surgery). AIM: Assessment of the effectiveness of a comprehensive treatment protocol for LUTS in primary care. DESIGN OF STUDY: Randomised controlled trial. SETTING: Fourteen general practices in the Netherlands. METHOD: Intervention: treatment protocol based on a formalised expert opinion. Control condition: usual care. Study population: 208 subjects with moderate to severe LUTS (IPSS > or =8, median = 13). OUTCOME MEASURES: symptom severity (IPSS [International Prostate Symptom Score]), bother score (Dan-PSS [Danish Prostate Symptom Score]), and maximum urinary flow (Q(max)); incidence of acute urinary retention and urinary tract infections. RESULTS: In the intervention group markedly more subjects used an alpha-blocker at end of follow-up than in the usual care group (24% versus 6%). No significant differences were found between intervention and control group in IPSS, Q(max) or Dan-PSS. CONCLUSION: alpha-blockers and watchful waiting are the most frequent treatment modalities for LUTS in primary care. Our study showed no evidence that a protocol using well-defined indications for all possible treatment modalities based on a formalised expert opinion procedure has added value. Based on our results, we cannot recommend a broadening of the indication for alpha-blockers, which, however, seems to be the current trend. 相似文献
20.
Evaluation of urethral pressure profilometry for the diagnosis of genuine stress incontinence 总被引:2,自引:1,他引:1
Summary Given the expense of radiographic imaging facilities and the reproducibility of urethral pressure measurements with microtransducers, the use of urethral pressure profilometry (UPP) has been gaining widespread popularity for the diagnosis of genuine stress incontinence (GSI). However, the clinical usefulness of the technique has not been adequately evaluated against the best available technique, namely videocystourethrography. Using the latter technique as the Gold Standard, the UPP results of 114 normal women and 95 GSI patients have been compared. In order to determine the most diagnostic UPP measure, 25 parameters were examined for each patient. With the use of the Kappa statistic it was found that the area under the stress profile was the most discriminatory of the UPP parameters. Even using this measure, the overlap between normal and GSI is so great as to make accurate diagnosis impossible. It is therefore concluded that UPP is useless for the diagnosis of GSI. 相似文献