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941.
Hashimoto D Ohmuraya M Hirota M Yamamoto A Suyama K Ida S Okumura Y Takahashi E Kido H Araki K Baba H Mizushima N Yamamura K 《The Journal of cell biology》2008,181(7):1065-1072
Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as a protector and killer of the cell depending on the stage of the disease or the surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70-77). We found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments. To analyze the role of macroautophagy in acute pancreatitis, we produced conditional knockout mice lacking the autophagy-related 5 gene in acinar cells. Acute pancreatitis was not observed, except for very mild edema in a restricted area, in conditional knockout mice. Unexpectedly, trypsinogen activation was greatly reduced in the absence of autophagy. These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome. 相似文献
942.
Ito Y Kanai T Totsuka T Okamoto R Tsuchiya K Nemoto Y Yoshioka A Tomita T Nagaishi T Sakamoto N Sakanishi T Okumura K Yagita H Watanabe M 《American journal of physiology. Gastrointestinal and liver physiology》2008,294(1):G199-G207
It has been recently demonstrated that NKG2D is an activating costimulatory receptor on natural killer (NK) cells, natural killer T (NKT) cells, activated CD8(+) T cells, and gammadelta T cells, which respond to cellular stress, such as inflammation, transformation, and infection. Here we show that intestinal inflammation in colitic SCID mice induced by adoptive transfer of CD4(+)CD45RB(high) T cells is characterized by significant increase of CD4(+)NKG2D(+) T cells and constitutive expression of NKG2D ligands, such as H60, Mult-1, and Rae-1, by lamina propria CD11c(+) dendritic cells. Furthermore, treatment with nondepleting and neutralizing anti-NKG2D MAb after transfer of CD4(+)CD45RB(high) T cells into SCID mice significantly suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of IFN-gamma by lamina propria CD4(+) T cells. These findings demonstrate that NKG2D signaling pathway is critically involved in CD4(+) T cell-mediated disease progression and suggest a new therapeutic target for inflammatory bowel diseases. 相似文献
943.
Developmental gene expression of gastrin receptor in rat stomach 总被引:10,自引:0,他引:10
He-Yao Wang Yoshikazu Kinoshita M. S Hassan Yumi Matsushima Hirokazu Fukui Toru Maekawa Akihiko Okada Shinya Waki Chiharu Kawanami Kiyohiko Kishi Makoto Watanabe Sakan Maeda Tsutomu Chiba 《Regulatory peptides》1997,70(2-3):183-189
Gastrin, which is present in fetal plasma, may have important roles in the development of gastric mucosa, since it is not only a potent stimulator of gastric acid secretion but also a growth promoting factor. Gastrin regulates various cellular functions via its receptors on cell membrane. Therefore, in order to elucidate a role for gastrin in the development of gastrointestinal system during gestation, Northern blot analysis was performed. The results of the study suggested that gastrin receptor is mainly present on parietal cells. Furthermore, proton pump and gastrin receptor gene expressions in parietal cells were strongly stimulated by the administration of exogenous gastrin. In conclusion, gastrin may be involved in the developmental change of parietal cells through its receptors. 相似文献
944.
Hiroharu Yamashita Keisuke Hata Hironori Yamaguchi Giichiro Tsurita Kanako Wake Soichi Watanabe Masao Taki Shoogo Ueno Hirokazu Nagawa 《Bioelectromagnetics》2010,31(7):573-575
The aim of this study was to elucidate the possible effects of short‐term exposure to a 1439‐MHz electromagnetic field (EMF) employing time division multiple access (TDMA), which is the basis of the Japanese Personal Digital Cellular system, on estrogenic activity in rats. Sixty‐four ovariectomized female Sprague–Dawley rats were divided into four groups: EMF exposure (EM), sham exposure, cage control, and 17 beta‐estradiol injected (E2). The EM group was exposed, for 4 h per day on three consecutive days, to the 1439‐MHz TDMA signal that produced 5.5–6.1 and 0.88–0.99 W/kg average specific absorption rates in the brain and the whole body, respectively. The uterine wet mass and serum estradiol level significantly increased in the E2 group, while there were no differences among the other three groups. Although negative effects of long‐term EMF exposure must be thoroughly investigated before a final conclusion can be reached, our results do not support the assumption that the high frequency EMF used in cellular phones exerts estrogenic activity. Bioelectromagnetics 31:573–575, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
945.
Kanamaru Y Sumiyoshi K Ushio H Ogawa H Okumura K Nakao A 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(7):4193-4197
Mast cells play an important role in innate immunity as well as in allergic reaction. However, regulatory mechanisms underlying mast cell-mediated innate immune responses remain largely unknown. Here we determined whether Smad3, a major signal transducer of TGF-beta, regulates innate immune response by mast cells against Gram-negative bacteria. Bone marrow-derived mast cells (BMMC) obtained from Smad3 null mutant mice showed augmented capacity to produce proinflammatory cytokines upon stimulation with a Gram-negative bacteria-associated product, LPS. In acute septic peritonitis model induced by cecal ligation and puncture, mast cell-deficient W/W(v) mice reconstituted with Smad3 null BMMC had significantly higher survival rate than W/W(v) mice reconstituted with wild-type BMMC, which was associated with higher production of proinflammatory cytokines in the peritoneal cavity. These in vitro and in vivo results suggest that Smad3 in mast cells functions as inhibitory for mast cell-mediated innate immune response against Gram-negative bacteria. Suppression of Smad3 expression in mast cells may thus have therapeutic potential for Gram-negative bacterial infection such as acute septic peritonitis by augmenting innate immune responses of mast cells. 相似文献
946.
Glyceride synthesis by four kinds of microbial lipase 总被引:2,自引:0,他引:2
Apart from their usual mechanism of action, lipases from Aspergillus niger and Rhizopus delemar also catalyzed the synthesis of glycerides from oleic acid and glycerol. Lipases from Geotrichum candidum and Penicillium cyclopium were inactivated by oleic acid, but were stable in the presence of casein, albumin or buffer of appropriate pH. Lipases from Aspergillus niger and Rhizopus delemar synthesized glycerides from, not only fatty acid, but dibasic acids and aromatic acids, making ester bonds only at position 1 and 3 of glycerol. In contrast, lipases from Geotricum candidum and Penicillium cyclopium synthesized glycerides only from long chain fatty acids, and made ester bonds at all three available positions of the glycerol molecule. 相似文献
947.
M Mikawa H Kato M Okumura M Narazaki Y Kanazawa N Miwa H Shinohara 《Bioconjugate chemistry》2001,12(4):510-514
Water-soluble gadolinium (Gd) endohedral metallofullerenes have been synthesized as polyhydroxyl forms (Gd@C(82)(OH)(n)(), Gd-fullerenols) and their paramagnetic properties were evaluated by in vivo as well as in vitro for the novel magnetic resonance imaging (MRI) contrast agents for next generation. The in vitro water proton relaxivity, R(1) (the effect on 1/T(1)), of Gd-fullerenols is significantly higher (20-folds) than that of the commercial MRI contrast agent, Magnevist (gadolinium-diethylenetriaminepentaacetic acid, Gd-DTPA) at 1.0 T close to the common field of clinical MRI. This unusually high proton relaxivity of Gd-fullerenols leads to the highest signal enhancement at extremely lower Gd concentration in MRI studies. The strong signal was confirmed in vivo MRI at lung, liver, spleen, and kidney of CDF1 mice after i.v. administration of Gd-fullerenols at a dose of 5 micromol Gd/kg, which was 1/20 of the typical clinical dose (100 micromol Gd/kg) of Gd-DTPA. 相似文献
948.
Pyrroloquinoline quinone (PQQ), which is an essential nutrient, has been shown to act as an antioxidant. Reactive oxygen species
(ROS) are thought to be responsible for neurotoxicity caused by the neurotoxin 6-hydroxydopamine (6-OHDA). In this study,
we investigated the ability of PQQ to protect against 6-OHDA-induced neurotoxicity using human neuroblastoma SH-SY5Y. When
SH-SY5Y cells were exposed to 6-OHDA in the presence of PQQ, PQQ prevented 6-OHDA-induced cell death and DNA fragmentation.
Flow cytometry analysis using the ROS-sensitive fluorescence probe, dihydroethidium, revealed that PQQ reduced elevation of
6-OHDA-induced intracellular ROS. In contrast to PQQ, antioxidant vitamins, ascorbic acid and α-tocopherol, had no protective effect. Moreover, we showed that PQQ effectively scavenged superoxide, compared to the antioxidant
vitamins. Therefore, our results suggest the protective effect of PQQ on 6-OHDA-induced neurotoxicity is involved, at least
in part, in its function as a scavenger of ROS, especially superoxide. 相似文献
949.
Epimorphin is involved in differentiation of rat hepatic stem-like cells through cell-cell contact 总被引:5,自引:0,他引:5
Miura K Nagai H Ueno Y Goto T Mikami K Nakane K Yoneyama K Watanabe D Terada K Sugiyama T Imai K Senoo H Watanabe S 《Biochemical and biophysical research communications》2003,311(2):415-423
Epimorphin, a mesenchymal cell surface-associated molecule, is detected on hepatic stellate cells (HSCs) in the liver. Here, we show the involvement of epimorphin in differentiation of rat hepatic stem-like cells (HSLCs) through contact with HSCs. HSLCs, isolated from adult rats, cultured in stellate cell-conditioned medium had no phenotypic and morphological changes, whereas HSLCs co-cultured with HSCs expressed albumin, transferrin, and tyrosine aminotransferase. An anti-epimorphin antibody inhibited hepatocytic differentiation of HSLCs in co-culture. Furthermore, epimorphin induced mRNA expression of albumin, transferrin, tyrosine aminotransferase, and gamma-glutamyl transpeptidase with decrease of c-kit and musashi-1. Morphologically, HSLCs piled up when co-cultured with HSCs, which was dramatically inhibited by an anti-epimorphin antibody. HSLCs contact with epimorphin started piling up, changed their shape from flat to cuboidal, and subsequently developed bile-canaliculi-like structures. In conclusion, epimorphin is a factor that induces differentiation of hepatic stem-like cells through epithelial-mesenchymal cell contact. 相似文献
950.
Metabolic and Biosynthetic Alterations in Cultured Astrocytes Exposed to Hypoxia/Reoxygenation 总被引:7,自引:0,他引:7
Osamu Hori Masayasu Matsumoto† Yusuke Maeda Hirokazu Ueda† Toshiho Ohtsuki David M. Stern† Taroh Kinoshita§ Satoshi Ogawa Takenobu Kamada 《Journal of neurochemistry》1994,62(4):1489-1495
To investigate the astrocyte response to hypoxia/reoxygenation, as a model relevant to the pathogenesis of ischemic injury, cultured rat astrocytes were exposed to hypoxia. On restoration of astrocytes to normoxia, there was a dramatic increase in protein synthesis within 3 h, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolically labeled astrocyte lysates showed multiple induced bands on fluorograms. Levels of cellular ATP declined during the first 3 h of reoxygenation and the concentration of AMP increased to ± 3.6 nmol/mg of protein within 1 h of reoxygenation. Reoxygenated astrocytes generated oxygen free radicals early after replacement into ambient air, and addition of diphenyliodonium, an NADPH oxidase inhibitor, diminished the generation of free radicals as well as the induction of several bands on fluorogram. Although addition of cycloheximide on reoxygenation resulted in inhibition of both astrocyte protein synthesis and accumulation of cellular AMP, it caused cell death within 6 h, suggesting the importance of protein synthesis in adaptation of hypoxic astrocytes to reoxygenation. Potential physiologic significance of biosynthetic products of astrocytes in hypoxia/reoxygenation was suggested by the recovery of glutamate uptake. These results indicate that the astrocyte response to hypoxia/reoxygenation includes generation of oxygen free radicals and de novo synthesis of products that influence cell viability and function in ischemia. 相似文献