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排序方式: 共有235条查询结果,搜索用时 15 毫秒
1.
Cytomegalovirus infection of the central nervous system stem cells from mouse embryo: a model for developmental brain disorders induced by cytomegalovirus 总被引:14,自引:0,他引:14
Kosugi I Shinmura Y Kawasaki H Arai Y Li RY Baba S Tsutsui Y 《Laboratory investigation; a journal of technical methods and pathology》2000,80(9):1373-1383
Cytomegalovirus (CMV) is the most frequent infectious cause of developmental disorders of the central nervous system (CNS) in humans. Infection of the CNS stem cells seems to be primarily responsible for the generation of the brain abnormalities. In this study, we evaluated the infectivity of murine CMV (MCMV) in epidermal growth factor (EGF)-responsive CNS stem cells prepared from fetal mouse brains, and studied the effect of infection on growth and differentiation of the stem cells. The CNS stem cells were permissive for MCMV infection, although MCMV replication was slower than in mouse embryonic fibroblasts. MCMV infection inhibited the growth and DNA replication of the stem cells. A clonogenic assay revealed that MCMV infection suppressed generation of colonies from single stem cells. When uninfected stem cells were induced to differentiate, a decrease in expression of the primitive neuroepidermal marker nestin was observed by immunocytochemistry and flow cytometry, whereas expression of neurofilament and glial fibrillary acidic protein (GFAP) were induced. In virus-infected CNS stem cells, nestin expression was retained, whereas the expression of neurofilament was more severely inhibited than that of GFAP in these cells. Two-color flow cytometry showed that differentiated glial precursor cells were preferentially susceptible to MCMV infection. MCMV-infected and uninfected CNS stem cells were transplanted into the neonatal rat brains. The reduced number of infected stem cells were engulfed into the subventricular zone and expressed GFAP, but did not migrate further, in contrast to the uninfected stem cells. These results suggest that suppression of the growth of the CNS stem cells and inhibition of the neuronal differentiation by CMV infection may be primary causes of disorders of brain development in congenital CMV infection. 相似文献
2.
A novel STK11 germline mutation in two siblings with Peutz-Jeghers syndrome complicated by primary gastric cancer 总被引:1,自引:0,他引:1
Shinmura K Goto M Tao H Shimizu S Otsuki Y Kobayashi H Ushida S Suzuki K Tsuneyoshi T Sugimura H 《Clinical genetics》2005,67(1):81-86
Patients with Peutz-Jeghers syndrome (PJS) are known to be at risk of gastric cancer (GC), and the STK11 gene is a susceptibility gene for PJS. However, as no cases of PJS with GC in which a STK11 germline mutation has been identified have ever been reported and other susceptibility genes have also been suggested to be involved in PJS, the relation between STK11 germline mutations and GC in PJS is still unknown. In this study, we used sequencing analysis to investigate the STK11, CDH1, and TP53 loci for a germline mutation in two siblings with PJS with primary GC. A novel type of the STK11 germline mutation, c.890delG, encoding a truncated protein (p.Arg297fsX38) was identified, but no germline mutations of the CDH1 and TP53 genes were detected. No inactivation of the wild-type allele by somatic mutation or chromosomal deletion or hypermethylation at the 5'-CpG site of STK11 was detected in the GC. This is the first report of a STK11 germline mutation in a PJS patient with GC and should contribute to establishing correlations between the STK11 germline mutations and GC in PJS patients. 相似文献
3.
RER phenotype and its associated mutations in familial gastric cancer 总被引:11,自引:1,他引:11
To clarify the genetic background of gastric cancer, we collected 28
familial gastric cancers (FGCs) with reference to the Amsterdam criteria in
hereditary non-polyposis colorectal cancer (HNPCC) and investigated the
frequency of replication error (RER) at six microsatellite loci and
frameshift mutations in its related genes in these tumors. RER was detected
in seven (25%) of the 28 gastric cancers. Five (18%) cases showed RER at
more than two loci. The apparent increased incidence of RER in FGC was not
detected compared with that reported in sporadic gastric cancers
previously. Among four cases with RER at more than three loci, frameshift
mutations in the (A)8 track of the hMSH3 gene were detected in all the four
cases and mutations in the (A)10 track of the transforming growth
factor-beta type II receptor (TGF-beta RII) gene were detected in the three
of them. Histologically, three of the four cases were of the intestinal
type, and the other one was the diffuse type. No mutation was detected in
the (C)8 and (GT)3 tracks of the hMSH6 and TGF-beta RII genes respectively.
These results indicate that the acquisition of the RER phenotype equally
influences the gastric carcinogenesis of both sporadic and familial cases,
and that the majority of FGC is pathogenetically distinct from HNPCC.
相似文献
4.
Infrequent Mutations of the hOGG1 Gene, That Is Involved in the Excision of 8-Hydroxyguanine in Damaged DNA, in Human Gastric Cancer 总被引:4,自引:0,他引:4
Kazuya Shinmura Takashi Kohno Hiroshi Kasai Kenji Koda Haruhiko Sugimura Jun Yokota 《Cancer science》1998,89(8):825-828
DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh8 Gua), which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9 gastric cancer cell lines and 35 primary gastric cancers for mutations and genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single strand conformation polymorphism analysis. A G-to-A transition was detected in a gastric cancer cell line, MKN1. This nucleotide change caused the conversion of the amino acid from Arg to His at codon 154, which is located in a domain highly conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected in primary gastric cancers. We compared the distribution of the polymorphic alleles associated with enzymatic activity (hOGG1-Ser326 vs. hOGG1-Cys326 ) between 35 gastric cancer patients and 42 healthy individuals. Although the frequency of the Cys326 allele, associated with low enzymatic activity, in gastric cancer patients was a little higher than that in healthy individuals, the difference did not reach statistical significance. These results suggest that low hOGG1 activity due to mutations and genetic polymorphisms is involved in the development of only a small subset of gastric cancers. 相似文献
5.
Otsubo S Tanabe K Shinmura H Ishikawa N Tokumoto T Hattori M Ito K Nitta K Akiba T Nihei H Toma H 《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》2004,8(4):299-304
In the present study, we reviewed the effect of post-transplant double filtration plasmapheresis (DFPP) on recurrent focal segmental glomerulosclerosis (FSGS) in the transplanted kidney allograft. Sixteen patients with post-transplant recurrent FSGS were enrolled in this study. Out of 16 patients with recurrent FSGS after transplantation, five did not receive DFPP and lost their grafts, while 11 did receive DFPP and four of these patients lost their grafts. Seven patients were able to maintain normal renal function for an average observation period of 57.1 +/- 40.7 months (range 7-125 months). In five patients who had a significant reduction in urinary protein after DFPP, the urinary protein level decreased from 26.60 +/- 23.05 g/day (range 3.34-62.6 g/day) to 2.95 +/- 3.42 g/day (range 0.02-8.64 g/day) and renal function was maintained. The beneficial effects of DFPP on graft outcome were more likely to occur if the patients experienced a marked drop in urinary excretion. Thus, post-transplant DFPP appears to be effective for reducing urinary protein levels and improving long-term graft survival. With the small numbers in this trial, however, none of the findings were statistically significant. We recommend the use of post-transplant DFPP to prevent the progression of recurrent FSGS. 相似文献
6.
7.
Ken Shinmura 《Heart failure reviews》2010,15(5):457-466
Adiponectin is an adipose tissue-derived adipokine abundant in human plasma. Increasing evidence from experimental studies suggests that adiponectin plays a protective role in the cardiovascular system. However, epidemiological studies revealed that high levels of adiponectin were associated with increased mortality and severity of congestive heart failure. Furthermore, several prospective studies indicated that high levels of adiponectin were positively correlated with increased total and cardiovascular disease mortality in the elderly. These results are completely opposite to our expectation based on the beneficial effects of adiponectin. Clinical observations demonstrated that plasma adiponectin levels were positively associated with B-type natriuretic peptide levels. Clinical and experimental studies indicated that the administration of atrial natriuretic peptide enhanced adiponectin production. It is still controversial whether increased adiponectin production is a bystander or a key mediator in the development of heart failure. However, recent investigations strongly suggest that increased adiponectin production in patients with heart failure is a part of compensatory mechanisms against oxidative stress and inflammation. In addition, complicated “adiponectin resistance” will accelerate a counter-regulatory increase in adiponectin in patients with advanced heart failure, although direct evidence that patients with heart failure have “adiponectin resistance” is still lacking. Increased adiponectin production might contribute, at least in part, to the metabolic and structural remodeling of the failing heart via activation of AMP-activated protein kinase and induction of cyclooxygenase-2. Further investigation is needed to clarify the exact role of increased adiponectin production under pathophysiological conditions. 相似文献
8.
9.
Downregulation of EphA7 by hypermethylation in colorectal cancer 总被引:7,自引:0,他引:7
Wang J Kataoka H Suzuki M Sato N Nakamura R Tao H Maruyama K Isogaki J Kanaoka S Ihara M Tanaka M Kanamori M Nakamura T Shinmura K Sugimura H 《Oncogene》2005,24(36):5637-5647
10.
Cyclooxygenase-2 (COX-2) is known to mediate the cardioprotective effects of the late phase of ischemic preconditioning (PC); however, the signaling pathways involved in COX-2 induction following ischemic PC are unknown. In addition, although inducible nitric oxide synthase (iNOS) has been identified as a co-mediator of late PC together with COX-2, the interaction between iNOS and COX-2 in the heart is unknown. Using conscious rabbits, we found that the induction of COX-2 expression 24 hours after ischemic PC was blocked by pretreatment with inhibitors of protein kinase C (PKC), Src protein tyrosine kinases (PTKs), and nuclear factor-kappaB (NF-kappaB) but not by inhibitors of NOS or scavengers of reactive oxygen species (ROS). The selective iNOS inhibitors SMT and 1400W, given 24 hours after PC, abrogated the increase in myocardial prostaglandin E2 (PGE2) and 6-keto-PGF1alpha, whereas the selective soluble guanylate cyclase inhibitor ODQ had no effect. COX-2 selective inhibitors (celecoxib and NS-398) did not affect iNOS activity. These results demonstrate that (i) ischemic PC upregulates cardiac COX-2 via PKC-, Src PTK-, and NF-kappaB-dependent signaling pathways, whereas generation of NO and ROS is not necessary, and (ii) the activity of newly synthesized COX-2 following PC requires iNOS-derived NO whereas iNOS activity is independent of COX-2-derived prostanoids, indicating that COX-2 is located downstream of iNOS in the protective pathway of late PC. The data also indicate that iNOS modulates COX-2 activity via cGMP-independent mechanisms. To our knowledge, this is the first demonstration that iNOS-derived NO drives prostanoid synthesis by COX-2 in the heart. NO-mediated activation of COX-2 may be a heretofore unrecognized mechanism by which NO exerts its salubrious effects in the late phase of PC. 相似文献