全文获取类型
收费全文 | 5162篇 |
免费 | 271篇 |
国内免费 | 127篇 |
专业分类
耳鼻咽喉 | 91篇 |
儿科学 | 35篇 |
妇产科学 | 48篇 |
基础医学 | 882篇 |
口腔科学 | 114篇 |
临床医学 | 529篇 |
内科学 | 976篇 |
皮肤病学 | 105篇 |
神经病学 | 457篇 |
特种医学 | 315篇 |
外科学 | 725篇 |
综合类 | 44篇 |
预防医学 | 207篇 |
眼科学 | 55篇 |
药学 | 498篇 |
中国医学 | 76篇 |
肿瘤学 | 403篇 |
出版年
2023年 | 27篇 |
2022年 | 161篇 |
2021年 | 239篇 |
2020年 | 107篇 |
2019年 | 121篇 |
2018年 | 151篇 |
2017年 | 124篇 |
2016年 | 195篇 |
2015年 | 344篇 |
2014年 | 354篇 |
2013年 | 384篇 |
2012年 | 566篇 |
2011年 | 537篇 |
2010年 | 271篇 |
2009年 | 246篇 |
2008年 | 329篇 |
2007年 | 313篇 |
2006年 | 244篇 |
2005年 | 168篇 |
2004年 | 112篇 |
2003年 | 99篇 |
2002年 | 87篇 |
2001年 | 80篇 |
2000年 | 69篇 |
1999年 | 44篇 |
1998年 | 39篇 |
1997年 | 27篇 |
1996年 | 15篇 |
1995年 | 16篇 |
1994年 | 14篇 |
1993年 | 17篇 |
1992年 | 17篇 |
1991年 | 11篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1977年 | 1篇 |
1976年 | 4篇 |
1975年 | 1篇 |
排序方式: 共有5560条查询结果,搜索用时 15 毫秒
21.
I. C. Park S. Y. Lee D. G. Jeon J. S. Lee C. S. Hwang B. G. Hwang S. H. Lee W. S. Hong S. I. Hong 《Journal of Korean medical science》1996,11(2):144-148
Cathepsin L is a kind of cystein proteases which are known to facilitate the invasion and metastasis of tumor cells by degrading the components of basement membrane and extracellular matrix. This study was undertaken to investigate the expression of cathepsin L by Northern blot analysis with radiolabeled cDNA specific for cathepsin L in six normal tissues, two osteosarcoma cell lines, MG-63 and Saos-2, six primary bone tumors and six metastatic bone tumors. In six normal tissues, the highest level of cathepsin L was expressed in liver with the descending order of liver > lung > thymus > ovary > kidney > esophagus. One of the two osteosarcoma cell lines established from the primary sites expressed a high level of cathepsin L mRNA. Out of six primary bone tumors, three (50%) expressed cathepsin L mRNA, while all (100%) of six metastatic bone tumors expressed the mRNA. These results demonstrating the higher frequency of expression of cathepsin L in metastatic bone tumors suggest that cathepsin L may participate in tumor invasion and metastasis. 相似文献
22.
Burwinkel B; Maichele AJ; Aagenaes O; Bakker HD; Lerner A; Shin YS; Strachan JA; Kilimann MW 《Human molecular genetics》1997,6(7):1109-1115
Glycogen storage disease due to phosphorylase kinase deficiency occurs in
several variants that differ in mode of inheritance and tissue-
specificity. This heterogeneity is suspected to be largely due to mutations
affecting different subunits and isoforms of phosphorylase kinase. The gene
of the ubiquitously expressed beta subunit, PHKB, was a candidate for
involvement in autosomally transmitted phosphorylase kinase deficiency of
liver and muscle. To identify such mutations, the complete PHKB coding
sequence was amplified by RT-PCR of RNA isolated from blood samples of
patients and analyzed by direct sequencing of PCR products. The
characterization of mutations was complemented by PCR of genomic DNA. In
one female and four male patients, we identified five independent nonsense
mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one
single-base insertion in codon N421, one splice-site mutation affecting
exon 31, and a large deletion involving the loss of exon 8. Although these
severe translation-disrupting mutations occur in constitutively expressed
sequences of the only known beta subunit gene of phosphorylase kinase,
PHKB, they are associated with a surprisingly mild clinical phenotype,
affecting virtually only the liver, and relatively high residual enzyme
activity of approximately 10%.
相似文献
23.
This study was designed to determine whether the somatostatin analogue,
octreotide, could prevent embryonic loss by normalizing increased uterine
insulin-like growth factor-I (IGF-I) action related to hyperoestrogenaemia
following superovulation. Superovulated immature and
oestradiol-17beta-treated adult rats were infused with 100 or 300 microg/ml
of octreotide respectively, or injected daily with 1 or 10 microg of
octreotide from day 1 to day 3 of pregnancy. On day 3, embryos were
collected from the oviducts and uteri. Uterine luminal fluid was subjected
to embryo culture. The amounts of uterine IGF-I and IGF binding proteins
(IGFBP) were determined by radioimmunoassay and ligand binding assay
respectively. Octreotide infusion normalized uterine IGF-I action following
superovulatory and oestradiol-17beta treatment, by reducing IGF-I
concentrations and increasing IGFBP concentrations. Octreotide infusion
increased the number of normal embryos by 2.7-fold and 1.7-fold in
superovulated and oestradiol-17beta- treated rats respectively, and
reversed the detrimental effects of uterine luminal fluid on embryonic
development caused by superovulatory and oestradiol-17beta treatment. Daily
injections with octreotide had similar but reduced effects in all
parameters examined in both treatment groups. In conclusion, octreotide may
reduce embryonic loss, at least in part, by normalizing IGF-I action
following superovulation.
相似文献
24.
25.
D. Han J. H. Sohn Y. J. Cho Y. C. Jeon H. J. Kim K. N. Park S. J. Chang 《Journal of Korean medical science》1997,12(5):465-468
A flat depressed early colon cancer (FDEC) is characterized by non-polypoid growth pattern, no association of adenomatous tissues and a tendency of even small lesions toward submucosal invasion and lymph node metastasis. It supports de novo carcinogenesis of colorectal cancer, although most colorectal cancers arise in pre-existing adenoma (adenoma-carcinoma sequence). There have been few reports of small depressed cancers because of the difficulty in colonoscopic detection and the rapid development to ulcerating advanced cancers. We report a case of flat depressed early colon cancer confined to mucosa detected by indigo carmine contrast colonoscopy. 相似文献
26.
Kang BS Chung TW Moon JY Lim JK Shon YH Nam KS Kim DS Jeon BH Kim CH 《Immunopharmacology and immunotoxicology》2004,26(3):355-372
Contribution of cytotoxic T lymphocytes (CTL) to experimental autoimmune thyroiditis (EAT) was well defined (Speidel et al., Eur. J. Immunol. 1997, 27, 2391-2399, Ref. 7). The native porcine thyroglobulin (pTg) showed high sensitivity to endo-o-N-acetylglucosaminidase F (Endo F) and its molecular weights, corresponding to about 330 kDa as a monomer and 660 kDa as a dimer, were reduced to smaller molecular weight forms by Endo F and trifluoromethanesulfonic acid (TMSF). Deglycosylated porcine Tg (dgpTg) and native pTg were injected i.v. into CBA/J mice, without the aid of adjuvants. Both lymphocytic infiltrations of the thyroid glands and levels of Tg-specific CTL were similar to those found in conventional EAT induced by Tg and adjuvants. In contrast, proliferative responses in native pTg and dgpTg-injected mice could not be detected, and titers of antibodies to pTg and dgpTg were 20 times and 30 times lower than that of pTg and adjuvants, respectively. The EAT-inducer CTL belonged to the CD8+ cell subset and exerted their thyroiditogenic potential through release of IFN-gamma. It was concluded that dgpTg-induced EAT is mediated by type 1 cytotoxic T cells (Tcl). Also, results that EAT induction of the glycosylated pTg (gpTg) was much lower than that of dgpTg, suggested that the abberant and incomplete glycosylation of the thyroglobulin is responsible for the induction of autoimmune thyroiditis. 相似文献
27.
DNA repair gene XRCC1 Arg399Gln polymorphism is associated with increased risk of uterine leiomyoma 总被引:2,自引:0,他引:2
Jeon YT Kim JW Park NH Song YS Kang SB Lee HP 《Human reproduction (Oxford, England)》2005,20(6):1586-1589
BACKGROUND: DNA repair gene XRCC1 Arg399Gln polymorphism has been associated with the risk of several human tumours. In the present study we investigated whether the XRCC1 polymorphism is related to the risk of uterine leiomyoma, the most common neoplasm of the female genital tract. METHODS: Three hundred and twenty-seven patients with uterine leiomyoma and 197 normal controls were enrolled, and XRCC1 genotyping was determined by PCR and restriction fragment length polymorphism. RESULTS: The proportions of individuals homozygous for 399Arg allele, heterozygous and homozygous for the 399Gln allele were 85.8%, 13.7% and 0.5% among the control group, and 46.2%, 53.2% and 0.6% in those with leiomyoma (P < 0.001), respectively. Logistic regression analysis (after adjusting for age, parity, menarche age and body mass index) showed a significant increased risk of uterine leiomyoma in women with the Arg/Gln genotype versus the Arg/Arg genotype (odds ratio 6.79; 95% confidence interval 4.20-10.99; P < 0.001). CONCLUSIONS: In Korean women, the 399Gln polymorphism of XRCC1 is associated with an increased risk of uterine leiomyoma. 相似文献
28.
Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency 总被引:1,自引:0,他引:1
Hong YS; Kerr DS; Craigen WJ; Tan J; Pan Y; Lusk M; Patel MS 《Human molecular genetics》1996,5(12):1925-1930
An infant girl with elevated blood lactate, pyruvate, and plasma
branched-chain amino acids was diagnosed with dihydrolipoamide
dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4)
deficiency. Activities of the pyruvate dehydrogenase complex and E3 from
patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in
cultured skin fibroblasts, respectively. Western blot analysis demonstrated
that the amount of E3 protein in fibroblasts from the patient and her
father was about half of controls, while Northern blot analysis showed
normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs
from the patient revealed two mutations in separate alleles. One is a
single base insertion of an extra adenine in the last codon of the leader
peptide sequence (TAC-->TAAC) leading to a nonsense mutation which
results in the premature termination of the precursor E3 polypeptide
(Y35X). The other is a missense mutation due to substitution of guanine for
adenine, causing an Arg-->Gly substitution at amino acid 460 of the
mature protein (R460G) which triggers the loss of E3 activity probably by
structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the
parents demonstrated that the nonsense mutation was inherited from the
father and the missense mutation was inherited from the mother.
相似文献
29.
Won MH Kang T Park S Jeon G Kim Y Seo JH Choi E Chung M Cho SS 《Neuroscience letters》2001,301(2):139-142
Delayed neuronal death in the CA1 of the hippocampus following global ischemia has been evoked by both the activation of N-methyl-D-aspartate receptor (NR) and the generate reactive oxygen species in the neurons. In the present study, we investigated whether oxidative DNA damages may be correlated with NR subunits (NR1 and NR2A/B) expression following ischemia insults in vivo. Thirty minutes after ischemia-reperfusion, the intensities of both NR and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivities were markedly increased in neurons of CA1. However, NR2A/B and 8-OHdG immunoreactivities were enhanced in CA1 over 24 h after ischemia although NR1 immunoreactivity was decreased. These results suggest that oxidative stress and excitotoxicity in the CA1 may simultaneously trigger neuronal damages at early time after ischemia, and free radical damage including oxidative DNA damage may eventually promote the delayed neuronal death in this region. 相似文献
30.
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