全文获取类型
收费全文 | 2254篇 |
免费 | 140篇 |
国内免费 | 38篇 |
专业分类
耳鼻咽喉 | 47篇 |
儿科学 | 80篇 |
妇产科学 | 22篇 |
基础医学 | 387篇 |
口腔科学 | 57篇 |
临床医学 | 227篇 |
内科学 | 396篇 |
皮肤病学 | 117篇 |
神经病学 | 181篇 |
特种医学 | 213篇 |
外国民族医学 | 1篇 |
外科学 | 331篇 |
综合类 | 41篇 |
预防医学 | 123篇 |
眼科学 | 24篇 |
药学 | 82篇 |
中国医学 | 1篇 |
肿瘤学 | 102篇 |
出版年
2022年 | 13篇 |
2021年 | 39篇 |
2020年 | 13篇 |
2019年 | 30篇 |
2018年 | 48篇 |
2017年 | 29篇 |
2016年 | 33篇 |
2015年 | 47篇 |
2014年 | 54篇 |
2013年 | 78篇 |
2012年 | 75篇 |
2011年 | 86篇 |
2010年 | 80篇 |
2009年 | 77篇 |
2008年 | 74篇 |
2007年 | 96篇 |
2006年 | 79篇 |
2005年 | 90篇 |
2004年 | 54篇 |
2003年 | 59篇 |
2002年 | 75篇 |
2001年 | 68篇 |
2000年 | 61篇 |
1999年 | 79篇 |
1998年 | 61篇 |
1997年 | 61篇 |
1996年 | 58篇 |
1995年 | 51篇 |
1994年 | 47篇 |
1993年 | 41篇 |
1992年 | 30篇 |
1991年 | 45篇 |
1990年 | 24篇 |
1989年 | 43篇 |
1988年 | 57篇 |
1987年 | 44篇 |
1986年 | 48篇 |
1985年 | 45篇 |
1984年 | 16篇 |
1979年 | 13篇 |
1977年 | 14篇 |
1976年 | 17篇 |
1975年 | 12篇 |
1973年 | 14篇 |
1972年 | 12篇 |
1971年 | 16篇 |
1968年 | 12篇 |
1967年 | 14篇 |
1913年 | 16篇 |
1912年 | 20篇 |
排序方式: 共有2432条查询结果,搜索用时 15 毫秒
21.
Direct in vivo observation of 5-fluorouracil release from a prodrug in human tumors heterotransplanted in nude mice: a magnetic resonance study 总被引:2,自引:0,他引:2
Guerquin-Kern JL Volk A Chenu E Lougerstay-Madec R Monneret C Florent JC Carrez D Croisy A 《NMR in biomedicine》2000,13(5):306-310
A glucuro-conjugated carbamate derivative of 5-fluorouracil (5-FU), originally designed as a prodrug for antibody-directed enzyme prodrug therapy (ADEPT) application, has been used for direct in vivo observation of in situ 5-FU generation in two human colon tumors heterotransplanted in nude mice. Because of the very fast elimination of glucuro-conjugated drugs, this observation required intratumoral injection. These tumors, when becoming necrotic, are rich enough in beta-glucuronidase to allow (19)F magnetic resonance spectroscopy monitoring, at the tumor level, of both prodrug elimination and 5-FU liberation without preliminary treatment by a specifically targeted enzyme conjugate. Convenient tumors have been selected by magnetic resonance imaging (MRI) on the basis of a correlative study between MRI and conventional histology. This contribution is the first report evidencing such a direct intra-tumoral conversion of a glucuro-conjugated prodrug into the expected active drug. This method, which should allow overall estimation of the beta-glucuronidase content of tumors, might also be helpful for selecting tumors as specific targets for non-toxic glucuro-conjugated prodrugs without prior treatment with a fusion protein. 相似文献
22.
Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders? 总被引:3,自引:2,他引:3
Based on cytogenetic observations, several syndromes have been previously
identified as microdeletion-based disorders. In this review, recent
progress is presented regarding whether one or multiple genes can be
implicated in the pathogenesis of these segmentally aneusomic syndromes.
The syndromes discussed include Angelman, Alagille, Williams,
Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and
DiGeorge/velocardiofacial or the 22q11 deletion syndromes. For Angelman and
Alagille syndromes, single genes have been identified, whereas for Williams
and Langer-Giedion syndromes, more than one gene can be implicated.
Although there has been significant progress in dissecting the molecular
basis for the other disorders, the ultimate answer regarding one versus
several genes remains to be determined.
相似文献
23.
Sydney S. Lazarus Barbara J. Wallace Bruno W. Volk 《The American journal of pathology》1962,41(5):579-591
24.
25.
Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy 总被引:2,自引:0,他引:2
Pan TC; Zhang RZ; Pericak-Vance MA; Tandan R; Fries T; Stajich JM; Viles K; Vance JM; Chu ML; Speer MC 《Human molecular genetics》1998,7(5):807-812
The Bethlem myopathy is a rare autosomal dominant proximal myopathy
characterized by early childhood onset and joint contractures. Evidence for
linkage and genetic heterogeneity has been established, with the majority
of families linked to 21q22.3 and one large family linked to 2q37,
implicating the three type VI collagen subunit genes, COL6A1 (chromosome
21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes.
Mutations of the invariant glycine residues in the triple-helical
domain-coding region of COL6A1 and COL6A2 have been reported previously in
the chromosome 21-linked families. We report here the identification of a
G-->A mutation in the N-terminal globular domain-coding region of COL6A3
in a large American pedigree (19 affected, 12 unaffected), leading to the
substitution of glycine by glutamic acid in the N2 motif, which is
homologous to the type A domains of the von Willebrand factor. This
mutation segregated to all affected family members, to no unaffected family
members, and was not identified in 338 unrelated Caucasian control
chromosomes. Thus mutations in either the triple-helical domain or the
globular domain of type VI collagen appear to cause Bethlem myopathy.
相似文献
26.
doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH) 总被引:12,自引:0,他引:12
des Portes V; Francis F; Pinard JM; Desguerre I; Moutard ML; Snoeck I; Meiners LC; Capron F; Cusmai R; Ricci S; Motte J; Echenne B; Ponsot G; Dulac O; Chelly J; Beldjord C 《Human molecular genetics》1998,7(7):1063-1070
Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical
dysgenesis disorder associated with a defect in neuronal migration.
Clinical manifestations are epilepsy and mental retardation. This disorder,
which mainly affects females, can be inherited in a single pedigree with
lissencephaly, a more severe disease which affects the male individuals.
This clinical entity has been described as X- SCLH/LIS syndrome. Recently
we have demonstrated that the doublecortin gene, which is localized on the
X chromosome, is implicated in this disorder. We have now performed a
systematic mutation analysis of doublecortin in 11 unrelated females with
SCLH (one familial and 10 sporadic cases) and have identified mutations in
10/11 cases. The sequence differences include nonsense, splice site and
missense mutations and these were found throughout the gene. These results
provide strong evidence that loss of function of doublecortin is the major
cause of SCLH. The absence of phenotype-genotype correlations suggests that
X-inactivation patterns of neuronal precursor cells are likely to
contribute to the variable clinical severity of this disorder in females.
相似文献
27.
Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR). 总被引:28,自引:1,他引:28 下载免费PDF全文
Cytokines serve a central function as key factors in the regulation of the intestinal immune response and mediation of tissue damage in inflammatory bowel disease (IBD). Abnormalities in the expression of immunoregulatory cytokines such as IL-2, IL-4, IL-10 and interferon-gamma (IFN-gamma) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. Therefore, cytokine mRNA concentrations were determined in the mucosa of patients with IBD at sites of active (n = 13) and inactive (n = 12) ulcerative colitis (UC), active (n = 11) and inactive (n = 11) Crohn's disease (CD) and in control patients (n = 14) using quantitative RT-PCR. IL-10 mRNA concentrations were significantly increased in patients with both active UC (P < 0.001) and active CD (P < 0.005) compared with control patients. IFN-gamma mRNA concentrations were also significantly increased both in patients with active UC (P < 0.02) and active CD (P < 0.05) compared with control patients, whereas IL-2 mRNA levels were significantly (P < 0.02) increased only in active CD. IL-4 mRNA expression in the intestinal mucosa was frequently below the detection limit. Our results demonstrate that chronic intestinal inflammation in patients with CD is characterized by an increase of Th1-like cytokines. Furthermore, the increased IL-10 mRNA expression at sites of active IBD suggests that IL-10 is an important regulatory component involved in the control of the inflammatory response in inflammatory bowel disease. 相似文献
28.
Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12) 总被引:15,自引:0,他引:15
C Turc-Carel A Aurias F Mugneret S Lizard I Sidaner C Volk J P Thiery S Olschwang I Philip M P Berger 《Cancer Genetics and Cytogenetics》1988,32(2):229-238
Since our initial reports on chromosomal studies in eight Ewing's sarcomas (ES), we have carried out similar investigations on 23 additional ES specimens following short-term culture of tumor cells (16 cases), and established in vitro cell lines (three cases) and on xenografted tumors in nude mice (four cases). We demonstrated the presence of the reciprocal t(11;22)(q24;q12) in every case except one that exhibited a complex t(11;22;14)(q24;q12;q11). On the basis of results from these additional 23 cases, we confirm the consistency of the t(11;22)(q24;q12) in ES. Moreover, we reviewed 54 ES cases reported by other investigators; when added to our 31 cases, this brings the total number to 85 unrelated cases of ES available for an evaluation of the frequency of involvement of bands 11q24 and 22q12 in translocations in ES. The standard t(11;22)(q24;q12) proved to be a remarkably consistent event, present in 83% of the cases. Five percent of the cases exhibited complex translocations involving a third chromosome in addition to chromosomes #11 and #22. In 4% of the cases variant translocations involved 22q12 but with a chromosome(s) other than #11. The breakpoint on chromosome 22q12 appears to be the most consistently observed event in 92% of the cases, whereas, the breakpoint at chromosome 11q24 was observed in 88% of the cases. 相似文献
29.
Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Human Brain Tumors 总被引:16,自引:0,他引:16 下载免费PDF全文
Klaus Lampert Uwe Machein Mrcia Regina Machein Walter Conca Hans Hartmut Peter Benedikt Volk 《The American journal of pathology》1998,153(2):429-437
In this study, we investigated the expression patterns of 15 matrix metalloproteinases (MMPs) and three tissue inhibitors of metalloproteinase in gliomas, medulloblastomas, and normal brain tissue. By Northern blot analysis we found increased levels of mRNAs encoding for gelatinase A, gelatinase B, two membrane-type MMPs (mt1- and mt2-MMP), and tissue inhibitors of metalloproteinase-1 in glioblastomas and medulloblastomas. We observed a significant increase of mt1-MMP, gelatinase A, gelatinase B, and tissue inhibitors of metalloproteinase-1 in glioblastomas as compared with low-grade astrocytomas, anaplastic astrocytomas, and normal brain. In medulloblastomas, the expression of mt1-MMP, mt2-MMP, and gelatinase A were also increased, but to a lesser extent than that observed in glioblastomas. These data were confirmed at the protein level by immunostaining analysis. Moreover, substrate gel electrophoresis showed that the activated forms of gelatinases A and B were present in glioblastomas and medulloblastomas. These results suggest that increased expression of mt1-MMP/gelatinase A is closely related to the malignant progression observed in gliomas. Furthermore, the present study demonstrates, to our knowledge for the first time, that medulloblastomas express high levels of MMP. 相似文献
30.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献