全文获取类型
收费全文 | 1592篇 |
免费 | 133篇 |
国内免费 | 23篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 44篇 |
妇产科学 | 55篇 |
基础医学 | 261篇 |
口腔科学 | 9篇 |
临床医学 | 167篇 |
内科学 | 379篇 |
皮肤病学 | 30篇 |
神经病学 | 189篇 |
特种医学 | 98篇 |
外科学 | 188篇 |
综合类 | 15篇 |
预防医学 | 77篇 |
眼科学 | 9篇 |
药学 | 68篇 |
肿瘤学 | 155篇 |
出版年
2023年 | 9篇 |
2022年 | 5篇 |
2021年 | 43篇 |
2020年 | 24篇 |
2019年 | 22篇 |
2018年 | 36篇 |
2017年 | 25篇 |
2016年 | 37篇 |
2015年 | 48篇 |
2014年 | 53篇 |
2013年 | 65篇 |
2012年 | 101篇 |
2011年 | 110篇 |
2010年 | 82篇 |
2009年 | 64篇 |
2008年 | 111篇 |
2007年 | 123篇 |
2006年 | 97篇 |
2005年 | 78篇 |
2004年 | 71篇 |
2003年 | 75篇 |
2002年 | 76篇 |
2001年 | 12篇 |
2000年 | 14篇 |
1999年 | 15篇 |
1998年 | 29篇 |
1997年 | 30篇 |
1996年 | 21篇 |
1995年 | 20篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 10篇 |
1991年 | 15篇 |
1990年 | 11篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 14篇 |
1986年 | 35篇 |
1985年 | 13篇 |
1984年 | 9篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1979年 | 5篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1974年 | 3篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 5篇 |
1969年 | 4篇 |
排序方式: 共有1748条查询结果,搜索用时 31 毫秒
11.
12.
Germline mutations of the CDKN2 gene in UK melanoma families 总被引:4,自引:1,他引:4
Harland M; Meloni R; Gruis N; Pinney E; Brookes S; Spurr NK; Frischauf AM; Bataille V; Peters G; Cuzick J; Selby P; Bishop DT; Bishop JN 《Human molecular genetics》1997,6(12):2061-2067
Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin
D kinase inhibitor p16, and more rarely, mutations in the gene coding for
CDK4, the protein to which p16 binds, underlie susceptibility in some
melanoma families. We have sequenced all exons of CDKN2 and analysed the
CDK4 gene for mutations in 27 UK families showing evidence of
predisposition to melanoma. Five different germline mutations in CDKN2 were
found in six families. Three of the mutations (Met53Ile, Arg24Pro and
23ins24) have been reported previously. We have identified two novel CDKN2
mutations (88delG and Ala118Thr) which are likely to be associated with the
development of melanoma, because of their co-segregation with the disease
and their likely functional effect on the CDKN2 protein. In binding assays
the protein expressed from the previously described mutation, Met53Ile, did
not bind to CDK4/CDK6, confirming its role as a causal mutation in the
development of melanoma. Ala118Thr appeared to be functional in this assay.
Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were
detected in exon 2 of CDK4, suggesting that causal mutations in this gene
are uncommon. The penetrance of these mutant CDKN2 genes is not yet
established, nor is the risk of non-melanoma cancer to gene carriers.
相似文献
13.
Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP) 总被引:8,自引:0,他引:8
Rowe PS; Oudet CL; Francis F; Sinding C; Pannetier S; Econs MJ; Strom TM; Meitinger T; Garabedian M; David A; Macher MA; Questiaux E; Popowska E; Pronicka E; Read AP; Mokrzycki A; Glorieux FH; Drezner MK; Hanauer A; Lehrach H; Goulding JN; O'Riordan JL 《Human molecular genetics》1997,6(4):539-549
Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with
homologies to endopeptidases, on the X-chromosome), are responsible for
X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family
of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has
raised important questions regarding PEX function at the molecular level.
The aim of this study was to analyse 99 HYP families for PEX gene
mutations, and to correlate predicted changes in the protein structure with
Zn2+ metallopeptidase gene function. Primers flanking 22 characterised
exons were used to amplify DNA by PCR, and SSCP was then used to screen for
mutations. Deletions, insertions, nonsense mutations, stop codons and
splice mutations occurred in 83% of families screened for in all 22 exons,
and 51% of a separate set of families screened in 17 PEX gene exons.
Missense mutations in four regions of the gene were informative regarding
function, with one mutation in the Zn2+-binding site predicted to alter
substrate enzyme interaction and catalysis. Computer analysis of the
remaining mutations predicted changes in secondary structure,
N-glycosylation, protein phosphorylation and catalytic site molecular
structure. The wide range of mutations that align with regions required for
protease activity in NEP suggests that PEX also functions as a protease,
and may act by processing factor(s) involved in bone mineral metabolism.
相似文献
14.
Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen,but not by the LACK antigen,are protective against experimental Leishmania (Leishmania) amazonensis infection
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Coelho EA Tavares CA Carvalho FA Chaves KF Teixeira KN Rodrigues RC Charest H Matlashewski G Gazzinelli RT Fernandes AP 《Infection and immunity》2003,71(7):3988-3994
Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-gamma) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN-gamma and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN-gamma and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis. 相似文献
15.
Hugues JN Soussis J Calderon I Balasch J Anderson RA Romeu A;Recombinant LH Study Group 《Human reproduction (Oxford, England)》2005,20(3):629-635
BACKGROUND: In anovulatory women undergoing ovulation induction, addition of recombinant human LH (rLH) to FSH treatment may promote the dominance of a leading follicle when administered in the late follicular phase. The objective of this study was to find the optimal dose of rLH that can maintain the growth of a dominant follicle, whilst causing atresia of secondary follicles. METHODS: Women with infertility due to anovulation and over-responding to FSH treatment were randomized to receive, in addition to 37.5 IU recombinant human FSH (rFSH), either placebo or different doses of rLH (6.8, 13.6, 30 or 60 microg) daily for a maximum of 7 days. The primary efficacy endpoint was the proportion of patients who had exactly one follicle > or = 16 mm on hCG day. RESULTS: Among 153 enrolled patients, the five treatment groups were similar in terms of baseline characteristics. The proportion of patients with exactly one follicle > or = 16 mm ranged from 13.3% in the placebo group to 32.1% in the 30 microg rLH group (P = 0.048). The pregnancy rate ranged from 10.3% in the 60 microg group to 28.6% in the 30 microg rLH group. Adverse events were similar between groups. CONCLUSIONS: In patients over-responding to FSH during ovulation induction, doses of up to 30 microg rLH/day appear to increase the proportion of patients developing a single dominant follicle (> or = 16 mm). Our data support the 'LH ceiling' concept whereby addition of rLH is able to control development of the follicular cohort. 相似文献
16.
Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers. 总被引:7,自引:0,他引:7
Hugues Legendre Christine Decaestecker Nathalie Nagy Alain Hendlisz Max-Peter Schüring Isabelle Salmon Hans-Joachim Gabius Jean-Claude Pector Robert Kiss 《Modern pathology》2003,16(5):491-504
This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated. 相似文献
17.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
18.
Albuquerque Lucas Alverne F. Almeida Joo Paulo de Macdo Filho Leonardo Jos Monteiro Joaquim Andrei F. Duffau Hugues 《Neurosurgical review》2021,44(3):1371-1389
Neurosurgical Review - There is a lack of class I evidence concerning the impact of surgery in the treatment of diffuse low-grade glioma; the early maximal resection with preservation of eloquent... 相似文献
19.
Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports 总被引:2,自引:3,他引:2
Aurousseau M.H.; Samama M.M.; Belhassen A.; Herve F.; Hugues J.N. 《Human reproduction (Oxford, England)》1995,10(1):94-97
Severe thrombotic events following ovarian stimulation for in-vitrofertilization (IVF) procedures in three women are reported.None of these patients presented any concomitant clinical signof ovarian hyperstimulation syndrome. Coagulation inhibitorswere in the normal range but cardiovascular risk factors werepresent. It is postulated that early thrombosis could be favouredby high endogenous plasma oestrogen concentrations subsequentto ovarian stimulation when associated with another risk factor.Our data are discussed in relation to previous publications.It is suggested that risk factors must be considered individuallybefore each IVF attempt. In patients at high risk, clinicalmanagement of the post-transfer period is recommended. 相似文献
20.