全文获取类型
收费全文 | 364篇 |
免费 | 53篇 |
国内免费 | 9篇 |
专业分类
426篇 |
出版年
2021年 | 7篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 15篇 |
2014年 | 21篇 |
2013年 | 14篇 |
2012年 | 13篇 |
2011年 | 20篇 |
2010年 | 15篇 |
2009年 | 11篇 |
2008年 | 10篇 |
2007年 | 19篇 |
2006年 | 13篇 |
2005年 | 11篇 |
2004年 | 5篇 |
2003年 | 11篇 |
2002年 | 13篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 10篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1993年 | 6篇 |
1992年 | 10篇 |
1991年 | 12篇 |
1990年 | 3篇 |
1989年 | 12篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 5篇 |
1985年 | 11篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 8篇 |
1980年 | 3篇 |
1979年 | 10篇 |
1978年 | 3篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 3篇 |
排序方式: 共有426条查询结果,搜索用时 10 毫秒
1.
肺癌在中国恶性肿瘤的发病率位居第一,随着低剂量薄层CT在肺癌筛查中的广泛应用,临床发现更多表现为非完全实性结节的肺腺癌,目前众多研究使CT影像学特征和肺腺癌病理的关系得到更进一步的认知,虽然CT能对部分非完全实性结节做出定性和定位诊断,但仍有部分非完全实性结节诊断困难,PET-CT结合了病灶的代谢信息和精确的定位信息,从而提高对肺部结节诊断的敏感性、特异性、准确性,综合多个文献PET-CT在非完全实性结节中的诊断分期价值较CT无明显提升,却在评估预后和制定合适手术方案上可以起到一定的作用,本文就PET-CT在SSN中的应用价值进行阐述。 相似文献
2.
Chondroid bone arises from mesenchymal stem cells in organ culture of mandibular condyles 总被引:1,自引:0,他引:1
M Silbermann A H Reddi A R Hand R Leapman K von der Mark A Franzen 《Journal of craniofacial genetics and developmental biology》1987,7(1):59-79
Mandibular condyles of fetal mice 19 to 20 days in utero comprising clean cartilage and its perichondrium were cultured for up to 14 days, and their capacity to develop osteoid and to mineralize in vitro was examined. After 3 days in culture the cartilage of the mandibular condyle appeared to have lost its inherent structural characteristics, including its various cell layers: chondroprogenitor, chondroblastic, and hypertrophic cells. At that time interval no chondroblasts could be seen; instead, most of the cartilage consisted of hypertrophic chondrocytes. By that time, the surrounding perichondrium, which contains pluripotential mesenchymal stem cells, revealed the first signs of extracellular matrix enclosing type I collagen, bone alkaline phosphatase, osteonection, fibronectin, and bone sialoprotein as demonstrated by immunofluorescent techniques. Electron microscopic examinations of the newly formed matrix revealed foci of mineralization within and along collagen fibers as is normally observed during bone development. The composition of the latter mineral deposits resembled calcium pyrophosphate crystals. Following 14 days in culture larger portions of the condyle revealed signs of osseous matrix, yet the tissue reacted positively for type II collagen. Hence, the condylar cartilage, a genuine representative of secondary-type cartilage, elaborated in vitro a unique type of bone that would be most appropriately defined as chondroid bone. Biochemical assays indicated that the de novo formation of chondroid bone was correlated with changes in alkaline phosphatase activity and 45Ca incorporation. The findings of the present study imply that mesenchymal stem cells that ordinarily differentiate into cartilage possess the capacity to differentiate into osteogenic cells and form chondroid bone. 相似文献
3.
Jorge E. Moreira Arthur R. Hand L. A. Håkan Borg Stellan Sandler Michael Welsh Nils Welsh Décio L. Eizirik 《Virchows Archiv. B, Cell pathology including molecular pathology》1991,60(1):337-344
We have previously described a preferential reduction in the secretory response to nutrient secretagogues in pancreatic mouse
islets maintained in culture after in vitro exposure to streptozotocin (SZ). This reduction was associated with an impaired
substrate metabolism at the mitochondrial level. To further clarify this issue, mouse pancreatic islets were exposed in vitro
to 2.2 mM SZ for 30 min. At 4 h after SZ treatment ultrastructural changes were apparent in the endoplasmic reticulum and
Golgi areas of the B-cells. However, 2 and 6 days following SZ exposure the B-cells appeared well preserved, except for a
marked decrease in the number of insulin-containing secretory granules. A morphometric analysis of the B-cells 6 days after
SZ exposure showed a normal B-cell size and a normal volume fraction of B-cell mitochondria. However, there was a decrease
in total islet size and a 13% decrease in the volume fraction of B-cells in the islets. These mouse islets exhibited a decreased
content of the mitochondrial DNA-encoded cytochrome b mRNA, as evaluated by dot-blot analysis. As a whole, the data obtained
indicate that SZ treatment does not induce a decrease in the number of mitochondria or long-lasting ultrastructural damage
to this organelle. However, there is a clear decrease in the cytochrome b mRNA, suggesting that SZ can induce damage to the
mitochondrial DNA. 相似文献
4.
5.
M I Mednieks R A Jungmann C Fischler A R Hand 《The journal of histochemistry and cytochemistry》1989,37(3):339-346
A mouse monoclonal antibody of the IgM class, MAb BB1, specific for the type II regulatory subunit (RII) of cyclic AMP-dependent protein kinase (cAPK), was produced using a purified subcellular protein fraction from rat parotid gland as the original antigen. The antibody immunoprecipitated radioactivity labeled RII from bovine heart cAPK, and from rat and human parotid saliva. Western blot analysis revealed specific binding of the antibody to proteins of 52 and 54 KD in extracts of rat parotid tissue, parotid saliva, and bovine heart cAPK. Immunogold labeling of thin sections of rat parotid gland revealed specific labeling of acinar cell nuclei (especially the heterochromatin), cytoplasm (particularly in areas containing granular endoplasmic reticulum), and the content of secretory granules. Labeling was greatly reduced (approximately 84%) when the antibody was pre-absorbed with an excess of bovine heart cAPK. In duct cells the cytoplasm and nuclei were also labeled, but few gold particles were present over secretory granules. These results provide additional evidence for the presence of nuclear cAPK in rat parotid cells, and confirm previous observations on the presence of cAPK regulatory subunits in acinar secretory granules and saliva. The hybridoma reagent will be used for studies of stimulus responses in the parotid and for immunocytochemical analyses of RII distribution in other secretory tissues. 相似文献
6.
7.
We have investigated the effect of the nucleoside analogue 5,6-dichloro-1-β-
-ribofuranosyl-benzimidazole (DRB) on DNA synthesis in the L-929 line of mouse fibroblasts. Earlier studies have shown that this compound selectively inhibits the synthesis of a major fraction of nuclear heterogeneous RNA (hnRNA). At 60–75 μM, DRB decreases the rate of nuclear hnRNA synthesis by two-thirds and prevents the appearance in the cytoplasm of almost all poly(A)-containing messenger RNA (mRNA). At similar dose levels, DRB inhibits the overall rate of DNA synthesis as measured by thymidine incorporation by only 20% (after correction for decreased thymidine uptake into total cellular material). Analyses of density gradients of BUdR and [3H]thymidine-substituted DNA and of autoradiograms of extended fibers of [3H]thymidine-labeled DNA confirm this inhibition and suggest that DRB acts on DNA solely by reducing the rate of replication fork movement. The apparent size of replication units is unchanged by drug treatment. DRB also inhibits the transport of thymidine into cells. As determined by kinetic studies of thymidine uptake, transport is inhibited competitively by drug treatment. Several other aspects of thymidine metabolism are not affected by DRB. It does not alter the size of the total dTTP pool, and there is no breakdown of template DNA in DRB-treated cells. 相似文献
8.
The present electron microscopic cytochemical investigation was undertaken to characterize the alterations in the golgi apparatus and GERL of rat parotid acinar cells during ethionine intoxication and recovery. Although the Golgi apparatus and GERL were reduced in size, and some broadening of the Golgi saccules occurred as the result of ethionine treatment, the relative localization of thiamine pyrophosphatase (TPPase) activity in the Golgi saccules, and acid phosphatase activity (AcPase) in GERL, remained unchanged. Shortly after ethionine treatment was stopped, a dramatic redistribution of enzyme activities was noted. Within the first 24 hours of recovery, the Golgi apparatus began to enlarge, and the content of secretory granules increased. By day 3 of recovery, cisternae morphologically identifiable as GERL and forming secretory granules possessed TPPase activity, while AcPase activity was virtually undetectable. After seven days of recovery, the Golgi apparatus and GERL appeared both morphologically and cytochemically normal. The enzyme modulation observed during recovery may be correlated with increased secretory granule production. Furthermore, the presence of TPPase activity in GERL and forming secretory granules lends support to the suggestion that GERL may be derived from the trans Golgi saccule. 相似文献
9.
We utilized quantitative electron microscopic immunogold labeling procedures to follow changes in the intragranular content of five secretory proteins of the rat submandibular gland (SMG) during and after chronic treatment with the beta-adrenergic agonist isoproterenol (IPR). Labeling intensities (gold particles/microns2) of acinar cell secretory granules for mucin and glutamine/glutamic acid-rich proteins, major secretory proteins of the normal SMG, showed opposite responses to IPR. Labeling intensities increased for mucin and decreased for glutamine/glutamic acid-rich proteins immediately after IPR injections began, then rapidly returned to control levels after cessation of IPR treatment. SMG Protein C immunoreactivity, found in both acinar and intercalated duct granules, was less affected by IPR. However, opposite changes in labeling intensity were observed between acinar and intercalated duct granules. Labeling intensities for proline-rich proteins, IPR-inducible secretory proteins, increased only after 10 days of stimulation and maintained a high level even after cessation of drug treatment. Type 2 cystatin, another IPR-inducible protein, increased gradually with chronic IPR treatment and decreased slowly during the recovery phase. These results suggest that chronic beta-adrenergic stimulation affects the expression of genes for several rat SMG secretory proteins in a different manner. 相似文献
10.
Suppression of bacterial cell wall-induced polyarthritis by recombinant gamma interferon 总被引:1,自引:0,他引:1
Group A streptococcal cell wall fragments (SCW) induce erosive polyarthritis, characterized by synovial cell hyperplasia and intense mononuclear cell infiltration, in susceptible rats. Because of the known antiproliferative and immunomodulatory effects of interferon (IFN), we evaluated the effect of systemically administered alpha, beta and gamma IFN on the evolution of these destructive lesions. Treatment with gamma IFN not only reduced the acute response, but had an even greater suppressive effect on the chronic mononuclear cell-mediated destructive phase of the disease (articular index 10.2 +/- 1.2 for SCW only versus 3.8 +/- 0.7 for SCW + gamma IFN; p less than 0.01). Treatment with gamma IFN was more effective in the suppression of the arthritis than alpha, beta IFN. Histopathologic evaluation of the joints demonstrated that gamma IFN-treated animals had significantly fewer inflammatory cells, and less synovial hyperplasia and erosions than the SCW controls. gamma IFN suppression of mononuclear cell prostaglandin synthesis and synovial fibroblast proliferation was consistent with its anti-arthritic effects. These data indicate that the pathophysiology of SCW-induced erosive polyarthritis is subject to regulatory control by gamma IFN and that the mechanisms of suppression may be relevant in the treatment of rheumatoid arthritis. 相似文献