全文获取类型
收费全文 | 803篇 |
免费 | 64篇 |
国内免费 | 1篇 |
出版年
2019年 | 5篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 13篇 |
2015年 | 19篇 |
2014年 | 16篇 |
2013年 | 63篇 |
2012年 | 31篇 |
2011年 | 43篇 |
2010年 | 27篇 |
2009年 | 20篇 |
2008年 | 36篇 |
2007年 | 47篇 |
2006年 | 40篇 |
2005年 | 38篇 |
2004年 | 36篇 |
2003年 | 28篇 |
2002年 | 38篇 |
2001年 | 39篇 |
2000年 | 32篇 |
1999年 | 22篇 |
1998年 | 10篇 |
1997年 | 11篇 |
1996年 | 6篇 |
1995年 | 9篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 15篇 |
1991年 | 15篇 |
1990年 | 15篇 |
1989年 | 10篇 |
1988年 | 15篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 11篇 |
1984年 | 12篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 8篇 |
1975年 | 4篇 |
1974年 | 8篇 |
1973年 | 8篇 |
1972年 | 6篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1965年 | 3篇 |
排序方式: 共有868条查询结果,搜索用时 15 毫秒
41.
BACKGROUND: Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC. CASE: A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen. CONCLUSION: Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism. 相似文献
42.
Hypoxia up-regulates glyceraldehyde-3-phosphate dehydrogenase in mouse brain capillary endothelial cells: involvement of Na+/Ca2+ exchanger 总被引:1,自引:0,他引:1
Yamaji R Fujita K Takahashi S Yoneda H Nagao K Masuda W Naito M Tsuruo T Miyatake K Inui H Nakano Y 《Biochimica et biophysica acta》2003,1593(2-3):269-276
43.
Hepatocyte growth factor enhances adhesion of breast cancer cells to endothelial cells in vitro through up-regulation of CD44 总被引:8,自引:0,他引:8
Mine S Fujisaki T Kawahara C Tabata T Iida T Yasuda M Yoneda T Tanaka Y 《Experimental cell research》2003,288(1):189-197
For cancer metastasis, tumor cells present in the circulation must first adhere to the endothelium. Integrins play a central role in leukocyte adhesion to the endothelium and subsequent migration into tissues. The majority of tumor cells derived from solid cancers, including breast cancer, do not express integrins. We investigated the mechanisms of adhesion and transendothelial migration of cancer cells using breast carcinoma cell lines. Our results showed the following features of breast cancer cells: (1) HGF stimulated breast cancer cells by up-regulating CD44 expression in a concentration-dependent manner. (2) the maximum level of HGF-induced CD44 up-regulation on breast cancer cell lines occurred within 3 h. (3) HGF-induced up-regulation of CD44 was mediated by the tyrosine kinase signaling pathway. (4) HGF induced CD44-mediated adhesion of tumor cell lines to bone marrow-derived endothelial cells. (5) HGF did not change rolling of breast cancer cell lines on bone marrow-derived endothelial cells, but enhanced firm adhesion of cancer cells on endothelial cells under shear stress conditions. (6) HGF increased transendothelial migration of cancer cells. Our results indicate that HGF stimulates CD44-mediated adhesion of breast cancer cells to bone marrow-derived endothelial cells, which subsequently results in transendothelial migration of tumor cells. These results suggest that CD44 may confer the metastatic properties of breast cancer cells and, therefore, could be used as a target in future molecular cancer therapy. 相似文献
44.
Yoneda F Moto T Sakae M Ohde H Knoll B Miklya I Knoll J 《Bioorganic & medicinal chemistry》2001,9(5):1197-1212
The catecholaminergic and serotoninergic neurons in the brain change their performance according to the physiological need via a catecholaminergic/serotoninergic activity enhancer (CAE/SAE) mechanism. Phenylethylamine (PEA), tyramine and tryptamine are the presently known endogenous CAE/SAE substances which enhance the impulse propagation mediated release of catecholamines and serotonin in the brain. A PEA derivative, (-)deprenyl (selegiline), known as a selective inhibitor of MAO-B, is for the time being the only CAE/SAE substance in clinical use. Aiming to develop a selective CAE/SAE substance much more potent than (-)deprenyl, a series of new 1-aryl-2-alkylaminoalkanes, structurally unrelated to PEA and the amphetamines, was designed and prepared. Among them, (-)1-(benzofuran-2-yl)-2-propylaminopentane ((-)BPAP) was selected as a promising candidate substance for further studies. (-)BPAP significantly enhanced in rats the impulse propagation mediated release of catecholamines and serotonin in the brain 30min after acute injection of 0.36nmol/kg sc. In the shuttle box, (-)BPAP was in rats about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance. (+/-)BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14)-10(-15)M concentration. 相似文献
45.
Oka T Yasusa T Ando T Watanabe M Yoneda F Ishida T Knoll J 《Bioorganic & medicinal chemistry》2001,9(5):1213-1219
Enantioselective synthesis and absolute configuration of (-)-1-(benzofuran-2-yl)-2-propylaminopentane ((-)-BPAP), which is a highly potent and selective catecholaminergic activity enhancer (CAE) substance, are described. The synthetic approach consists of the coupling reaction of benzofuran with (R)-N-tosyl-2-propylazirizine or (R)-N-methoxy-N-methylnorvaliamide, followed by appropriate modifications of the resulting coupling products. As the results, (-)-BPAP turned out to have the R configuration, which was finally confirmed by X-ray crystallographic analysis. 相似文献
46.
Circadian rhythm of atrioventricular conduction predicts long-term survival in patients with chronic atrial fibrillation 总被引:1,自引:0,他引:1
Hayano J Ishihara S Fukuta H Sakata S Mukai S Ohte N Kimura G 《Chronobiology international》2002,19(3):633-648
The R-R interval of the electrocardiogram during atrial fibrillation (AF) appears absolutely irregular. However, the Poincaré plot of the R-R interval reveals a sector shape of distribution that is unique to AF. Furthermore, the height of lower envelope (LE1.0) of the distribution and the degree of scatter above the envelope (scattering index) may reflect the refractoriness and concealment of atrioventricular (AV) conduction, respectively. We previously observed that both the LE1.0 and scattering index show clear circadian rhythms in patients with chronic AF and that the rhythms are blunted in those with congestive heart failure and chronic AF. In the present study, we examined if the blunted circadian rhythm of the AV conduction has prognostic value in patients with chronic AF. We studied a retrospective cohort of 120 patients who underwent 24h Holter monitoring at baseline. During an observation period of 33 +/- 16 mon, there were 25 deaths (21%) including 13 cardiac and 8 stroke deaths. All patients showed significant circadian rhythms in both LE1.0 and scattering index with acrophases occurring at night; however, patients dying subsequently from cardiac causes, but not those from fatal stroke were blunted in the circadian rhythms (the amplitudes were < 55% of those in surviving patients). Furthermore, the reduced circadian amplitude of scattering index was an increased risk for cardiac death even after adjustment of coexisting cardiovascular risks [adjusted relative risk (95% confidence interval) per 1-SD decrement, 4.24 (1.54-11.6)]. When patients were divided by the circadian amplitude of the scattering index of 36.5 msec (mean minus 1-SD), the 5yr cardiac mortality below and above the cutoff was 57 and 6%, respectively (log-rank test, p < 0.001). We conclude that the blunted circadian rhythm of AV conduction is an independent risk for cardiac death in patients with chronic AF. 相似文献
47.
Nishimura M Umehara H Nakayama T Yoneda O Hieshima K Kakizaki M Dohmae N Yoshie O Imai T 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(12):6173-6180
Fractalkine/CX3C ligand 1 and its receptor CX3CR1 are known to mediate both cell adhesion and cell migration. Here we show that CX3CR1 defines peripheral blood cytotoxic effector lymphocytes commonly armed with intracellular perforin and granzyme B, which include NK cells, gammadelta T cells, and terminally differentiated CD8(+) T cells. In addition, soluble fractalkine preferentially induced migration of cytotoxic effector lymphocytes. Furthermore, interaction of cytotoxic effector lymphocytes with membrane-bound fractalkine promoted subsequent migration to the secondary chemokines, such as macrophage inflammatory protein-1beta/CC ligand 4 or IL-8/CXC ligand 8. Thus, fractalkine expressed on inflamed endothelium may function as a vascular regulator for cytotoxic effector lymphocytes, regardless of their lineage and mode of target cell recognition, through its ability to capture them from blood flow and to promote their emigration in response to other chemokines. 相似文献
48.
Konishi A Shimizu S Hirota J Takao T Fan Y Matsuoka Y Zhang L Yoneda Y Fujii Y Skoultchi AI Tsujimoto Y 《Cell》2003,114(6):673-688
It is poorly understood how apoptotic signals arising from DNA damage are transmitted to mitochondria, which release apoptogenic factors into the cytoplasm that activate downstream destruction programs. Here, we identify histone H1.2 as a cytochrome c-releasing factor that appears in the cytoplasm after exposure to X-ray irradiation. While all nuclear histone H1 forms are released into the cytoplasm in a p53-dependent manner after irradiation, only H1.2, but not other H1 forms, induced cytochrome c release from isolated mitochondria in a Bak-dependent manner. Reducing H1.2 expression enhanced cellular resistance to apoptosis induced by X-ray irradiation or etoposide, but not that induced by other stimuli including TNF-alpha and UV irradiation. H1.2-deficient mice exhibited increased cellular resistance in thymocytes and the small intestine to X-ray-induced apoptosis. These results indicate that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following DNA double-strand breaks. 相似文献
49.
The origin of cortical microtubules (CMTs) was investigated in transgenic BY-2 cells stably expressing a GFP (green fluorescent protein) -tubulin fusion protein (BY-GT16). In a previous study, we found that CMTs were initially organized in the perinuclear regions but then elongated to reach the cell cortex where they formed bright spots, and that the appearance of parallel MTs from the bright spots was followed by the appearance of transverse MTs (Kumagai et al., Plant Cell Physiol. 42, 723-732, 2001). In this study, we investigated the migration of tubulin to the reorganization sites of CMTs at the M/G1 interface. After synchronization of the BY-GT16 cells by aphidicolin, the localization of GFP-tubulin was monitored and analyzed by deconvolution microscopy. GFP-tubulin was found to accumulate on the nuclear surface near the cell plate at the final stage of phragmoplast collapse. Subsequently, GFP-tubulin accumulated again on the nuclear surface opposite the cell plate, where nascent MTs elongated to the cell cortex. The significance of these observations on the mode of CMT organization is discussed. 相似文献
50.
Ueda A Nagase S Yokoyama H Tada M Noda H Ohya H Kamada H Hirayama A Koyama A 《Molecular and cellular biochemistry》2003,244(1-2):119-124
Spin probing methods using an electron spin resonance (ESR) spectrometer are used extensively and bring us a lot of information about in vivo redox mechanisms. However, the in vivo reducing mechanisms of exogenous nitroxide radicals, which serve as typical spin probing reagents are not clear. To clarify this, we examined the sequential kinetics of a spin probe, 4-hydroxy 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) in the in vivo organs, tissue homogenates and subcellular fractions of kidney and liver using an in vivo and X-band ESR spectrometers. As a parameter of reducing activity, we calculated the half-life of TEMPOL from the decay curve of ESR signal intensity. The half-life of TEMPOL in the whole organs and homogenates of the kidney was significantly shorter than that of the liver, this indicates that the kidney has more reducing activity against TEMPOL as compared to the liver. Subcellular fractional studies revealed that this reducing activity of the kidney mainly exists in the mitochondria. Contrarily, in addition to reduction in the mitochondria, TEMPOL in the liver was reduced by the microsome and cytosol. 相似文献