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91.
Dan N Kanai T Totsuka T Iiyama R Yamazaki M Sawada T Miyata T Yagita H Okumura K Watanabe M 《American journal of physiology. Gastrointestinal and liver physiology》2003,285(4):G754-G760
Fas/Fas ligand (FasL) interaction has been implicated in the pathogenesis of various diseases. To clarify the involvement of Fas/FasL in the pathogenesis of intestinal inflammation, we investigated the preventive and therapeutic effects of neutralizing anti-FasL monoclonal antibody (MAb) on the development of chronic colitis induced by adaptive transfer of CD4+CD45RBhigh T cells to SCID mice. Administration of anti-FasL MAb from 1 day after T cell transfer (prevention study) resulted in a significant improvement of clinical manifestations such as wasting and diarrhea. However, histological examination showed that mucosal inflammation in the colon, such as infiltration of T cells and macrophages, was not improved by the anti-FasL MAb treatment. In vitro studies showed that anti-FasL MAb did not inhibit IFN-gamma production by anti-CD3/CD28-stimulated lamina propria CD4+ T cells but suppressed TNF-alpha and IL-1beta production by lamina propria mononuclear cells. Therapeutic administration of anti-FasL MAb from 3 wk after T cell transfer also improved ongoing wasting disease but not intestinal inflammation. These results suggest that the Fas/FasL interaction plays a critical role in regulating systemic wasting disease but not local intestinal inflammation. 相似文献
92.
Okano-Uchida T Okumura E Iwashita M Yoshida H Tachibana K Kishimoto T 《The EMBO journal》2003,22(20):5633-5642
The Polo-like kinase, Plk, has multiple roles in regulating mitosis. In particular, Plk1 has been postulated to function as a trigger kinase that phosphorylates and activates Cdc25C prior to the activation of cyclin B-Cdc2 and thereby initiates its activation. However, the upstream regulation of Plk1 activation remains unclear. Here we have studied the interplay between Plk1 and Cdc2 through meiotic and early embryonic cycles in starfish. Distinct kinases, cyclin B-Cdc2, MAPK along with cyclin B- and/or cyclin A-Cdc2 and cyclin A-Cdc2, were unique upstream regulators for Plk1 activation at meiosis I, meiosis II and embryonic M-phase, respectively, indicating that Plk1 is not the trigger kinase at meiotic reinitiation. When Plk1 was required for cyclin B-Cdc2 activation, the action of Plk1 was mediated primarily through suppression of Myt1 rather than through activation of Cdc25. We propose that Plk1 can be activated by either cyclin A- or cyclin B-Cdc2, and its primary target is Myt1. 相似文献
93.
Molecular cloning of a cDNA encoding mouse DNA helicase B, which has homology to Escherichia coli RecD protein, and identification of a mutation in the DNA helicase B from tsFT848 temperature-sensitive DNA replication mutant cells
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Tada S Kobayashi T Omori A Kusa Y Okumura N Kodaira H Ishimi Y Seki M Enomoto T 《Nucleic acids research》2001,29(18):3835-3840
DNA helicase B is a major DNA helicase in mouse FM3A cells. A temperature-sensitive mutant defective in DNA replication, tsFT848, isolated from FM3A cells, has a heat-labile DNA helicase B. In this study, we purified DNA helicase B from mouse FM3A cells and determined partial amino acid sequences of the purified protein. By using a DNA probe synthesized according to one of the partial amino acid sequences, a cDNA was isolated, which encoded a 121.5 kDa protein containing seven conserved motifs for DNA/RNA helicase superfamily members. A database search revealed similarity between DNA helicase B and the α subunit of exodeoxyribonuclease V of a number of prokaryotes including Escherichia coli RecD protein, but no homologous protein was found in yeast. The cDNA encoding DNA helicase B from tsFT848 was sequenced and a mutation was found between DNA/RNA helicase motifs IV and V. 相似文献
94.
Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance 总被引:21,自引:0,他引:21
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Lee A Mao W Warren MS Mistry A Hoshino K Okumura R Ishida H Lomovskaya O 《Journal of bacteriology》2000,182(11):3142-3150
The effects of simultaneous expression of several efflux pumps on antibiotic resistance were investigated in Escherichia coli and Pseudomonas aeruginosa. Several combinations of efflux pumps have been studied: (i) simultaneous expression of a single-component efflux pump, which exports antibiotics into the periplasm, in combination with a multicomponent efflux pump that accomplishes efflux directly into the external medium; (ii) simultaneous expression of two single-component pumps; and (iii) simultaneous expression of two multicomponent pumps. It was found that when efflux pumps of different structural types were combined in the same cell (the first case), the observed antibiotic resistance was much higher than that conferred by each of the pumps expressed singly. Simultaneous expression of pairs of single-component or multicomponent efflux pumps (the second and third cases) did not produce strong increases in antibiotic resistance. 相似文献
95.
96.
97.
Furumoto Y Hiraoka S Kawamoto K Masaki S Kitamura T Okumura K Ra C 《Biochemical and biophysical research communications》2000,273(2):765-771
Genetic polyymorphisms that result in three amino acid changes in FcepsilonRI beta chain (Ile(181)-->Leu, Val(183)-->Leu, and Glu(237)-->Gly) have been identified as candidates that associate with allergic disorders such as atopy and asthma. To elucidate the biological significance of these polymorphisms in regulating the expression and function of FcepsilonRI, we generated four types of transfectants that express wild-type or mutant mouse beta chains corresponding to these human variants by retrovirus-mediated gene transfer into beta chain-deficient mouse-derived mast cells. No significant functional differences between the wild-type beta chain transfectant and any of the mutant beta chain transfectants were observed in beta-hexosaminidase release, intracellular calcium mobilization, or cytokine and leukotriene C(4) production in response to FcepsilonRI crosslinking. Our results suggest that these polymorphisms in FcepsilonRI beta chain do not affect FcepsilonRI-mediated mast cell activation at least in our mouse in vitro system. 相似文献
98.
Inhibition of food intake by central injection of anti-orexin antibody in fasted rats 总被引:8,自引:0,他引:8
Yamada H Okumura T Motomura W Kobayashi Y Kohgo Y 《Biochemical and biophysical research communications》2000,267(2):527-531
It has been shown that intracerebroventricular injection of synthetic orexins stimulated food intake in rats. This pharmacological evidence suggests that orexins may have a role for the central regulation of feeding. In the present study, we investigated the hypothesis of whether endogenous orexins indeed play a vital role in feeding behavior. An anti-orexin polyclonal antibody was used throughout the study. First, we examined the specificity of the antibody to orexin by Western blot analysis and immunohistochemistry. Next, the effects of central injection of the orexin antibody on food intake in 24-h-fasted rats were evaluated. Western blot analysis revealed that the orexin antibody detected synthetic orexin-A. Immunohistochemical study showed that orexin-positive neurons were identified only in the lateral hypothalamic area, in agreement with previous reports. Neither control antibody nor the orexin antibody preabsorbed with excess amount of orexin-A detected neurons, indicating that the orexin antibody is specific. Intracisternal but not intraperitoneal injection of the orexin antibody dose-dependently suppressed feeding. All these results suggest that immunoneutralization of endogenous orexins in the brain reduced food intake. In other words, we suggest that endogenous brain orexin may have a physiologically relevant action on feeding behavior. 相似文献
99.
Development of human T-cell leukemia virus type 1-transformed tumors in rats following suppression of T-cell immunity by CD80 and CD86 blockade
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Hanabuchi S Ohashi T Koya Y Kato H Takemura F Hirokawa K Yoshiki T Yagita H Okumura K Kannagi M 《Journal of virology》2000,74(1):428-435
Host immunity influences clinical manifestations of human T-cell leukemia virus type 1 (HTLV-1) infection. In this study, we demonstrated that HTLV-1-transformed tumors could develop in immunocompetent rats by blocking a costimulatory signal for T-cell immune responses. Four-week-old WKA/HKm rats were treated with monoclonal antibodies (MAbs) to CD80 and CD86 and subcutaneously inoculated with syngeneic HTLV-1-infected TARS-1 cells. During MAb treatment for 14 days, TARS-1 inoculation resulted in the development of solid tumors at the site of inoculation, which metastasized to the lungs. In contrast, rats not treated with MAbs promptly rejected tumor cells. Splenic T cells from MAb-treated rats indicated impairment of proliferative and cytotoxic T-lymphocyte responses against TARS-1 in vitro compared to untreated rats. However, tumors grown in MAb-treated rats regressed following withdrawal of MAb therapy. Recovery of TARS-1-specific T-cell immune responses was associated with tumor regression in these rats. Our results suggest that HTLV-1-specific cell-mediated immunity plays a critical role in immunosurveillance against HTLV-1-transformed tumor development in vivo. 相似文献
100.
Tomoo Kamiya A-Hon Kown Toshiki Kanemaki Yoichi Matsui Shouji Uetsuji Tadayoshi Okumura Yasuo Kamiyama 《In vitro cellular & developmental biology. Animal》1998,34(2):131-137
Summary The Anaeropack system for cell culture, which was originally designed for the growth of anaerobic bacteria, was used to produce
a hypoxic atmosphere for cultured hepatocytes. We measured changes in the oxygen and carbon dioxide concentrations and the
atmospheric temperature in an airtight jar. We also measured changes in the pH of the medium during hypoxia to assess the
accuracy of this system. Moreover, we used three durations (2, 3, and 4 h) of hypoxia and 8 h of reoxygenation in cultured
rat hepatocytes, and then measured the lactate dehydrogenase (LDH), ketone body concentration (acetoacetate + β-hydroxybutyrate),
and the ketone body ratio (KBR: acetoacetate/β-hydroxybutyrate) in the medium in order to assess the suitability of this system
as a model for reperfusion following liver ischemia. The oxygen concentration dropped to 1% or less within 1 h. The concentration
of carbon dioxide rose to about 5% at 30 min after the induction of the hypoxic conditions, and was maintained at this level
for 5 h. No effect of the reaction heat produced by the oxygen absorbent in the jar was recognized. The extent of cell injury
produced by changing the hypoxic parameters was satisfactorily reflected by the KBR, the ketone body concentration, and the
LDH activity released into the medium. Because this model can duplicate the conditions of the hepatocytes during revascularization
following ischemic liver, and the Anaeropack system for cell culture is easy to manipulate, it seems suitable for the experimental
study of hypoxic injury and revascularization in vitro. 相似文献