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81.
Aki Isobe Kenjiro Sawada Yasuto Kinose Chifumi Ohyagi-Hara Erika Nakatsuka Hiroshi Makino Tomonori Ogura Tomoko Mizuno Noriko Suzuki Eiichi Morii Koji Nakamura Ikuko Sawada Aska Toda Kae Hashimoto Seiji Mabuchi Tsuyoshi Ohta Ken-ichirou Morishige Hirohisa Kurachi Tadashi Kimura 《PloS one》2015,10(2)
Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment. 相似文献
82.
Akira Nakatsuma Mugiho Kaneda Hiromi Kodama Mika Morikawa Satoshi Watabe Kazunari Nakaishi Masakane Yamashita Teruki Yoshimura Toshiaki Miura Masaki Ninomiya Etsuro Ito 《PloS one》2015,10(6)
To reduce the window period between HIV-1 infection and the ability to diagnose it, a fourth-generation immunoassay including the detection of HIV-1 p24 antigen has been developed. However, because the commercially available systems for this assay use special, high-cost instruments to measure, for example, chemiluminescence, it is performed only by diagnostics companies and hub hospitals. To overcome this limitation, we applied an ultrasensitive ELISA coupled with a thio-NAD cycling, which is based on a usual enzyme immunoassay without special instruments, to detect HIV-1 p24. The p24 detection limit by our ultrasensitive ELISA was 0.0065 IU/assay (i.e., ca. 10-18 moles/assay). Because HIV-1 p24 antigen is thought to be present in the virion in much greater numbers than viral RNA copies, the value of 10-18 moles of the p24/assay corresponds to ca. 103 copies of the HIV-1 RNA/assay. That is, our ultrasensitive ELISA is chasing the detection limit (102 copies/assay) obtained by PCR-based nucleic acid testing (NAT) with a margin of only one different order. Further, the detection limit by our ultrasensitive ELISA is less than that mandated for a CE-marked HIV antigen/antibody assay. An additional recovery test using blood supported the reliability of our ultrasensitive ELISA. 相似文献
83.
Tetsu Yamane Masako Mitsumata Noriko Yamaguchi Tadao Nakazawa Kunio Mochizuki Tetsuo Kondo Tomonori Kawasaki Shin-ichi Murata Yoji Yoshida Ryohei Katoh 《Cell and tissue research》2010,340(3):471-479
Remodeling of endothelial basement membrane is important in atherogenesis. Since little is known about the actual relationship
between type IV collagen and matrix metalloprotease−2 (MMP-2) in endothelial cells (ECs) under shear stress by blood flow,
we performed quantitative analysis for type IV collagen and MMP-2 in ECs under high shear stress. The mRNA of type IV collagen
from ECs exposed to high shear stress (10 and 30 dyn/cm2) had a higher expression compared to ECs exposed to a static condition or low shear stress (3 dyn/cm2) (P < 0.01). 3H-proline uptake analysis and fluorography revealed a remarkable increase of type IV collagen under high shear stress (P < 0.01). In contrast, zymography revealed that exposing to high shear stress, however similar positivity was leveled in the
intracellular MMP-2 in the control and high shear stress-exposed ECs, reduced the secretion of MMP-2 in ECs. The results of
Northern blotting, gelatin zymography and monitoring the intracellular trafficking of GFP-labeled MMP-2 revealed that MMP-2
secretion by ECs was completely suppressed by high shear stress, but the intracellular mRNA expression, protein synthesis,
and transport of MMP-2 were not affected. In conclusion, we suggest that high shear stress up-regulates type IV collagen synthesis
and down-regulates MMP-2 secretion in ECs, which plays an important role in remodeling of the endothelial basement membrane
and may suppress atherogenesis. 相似文献
84.
Irie K Furukawa S Kadono T Kawano T 《Zeitschrift für Naturforschung. C, Journal of biosciences》2010,65(11-12):681-687
Some hundred cells of Chlorella-like green algae are naturally enclosed within the cytoplasm of a single cell of green paramecia (Paramecium bursaria). Therefore, P. bursaria serves as an experimental model for studying the nature of endo-symbiosis made up through chemical communication between the symbiotic partners. For studying the mechanism of symbiotic regulations, the materials showing successful symbiosis are widely used. Apart from such successful model materials, some models for symbiotic distortion would be of great interest in order to understand the nature of successful symbiosis. Here, we describe a case of unsuccessful symbiosis causing unregulated growth of algae inside the hosting ciliates. Recently, we have screened some cell lines, from the mass of P. bursaria cells survived after paraquat treatment. The resultant cell lines (designated as KMZ series) show novel and unusual morphological features with heavily darker green colour distinguishable from the original pale green-coloured paramecia. In this type of isolates, endo-symbiotic algae are restricted within one or two dense spherical structures located at the center of the host cells' cytoplasm. Interestingly, this isolate maintains the host cells' circadian mating response which is known as an alga-dependent behaviour in the host cells. In contrast, we discuss that KMZ lacks the host-dependent regulation of algal growth, thus the algal complex often over-grows obviously exceeding the original size of the normal hosting ciliates. Additionally, possible use of this isolate as a novel model for symbiotic cell-to-cell communication is discussed. 相似文献
85.
Hiroki Shimizu Shinji Tanaka Tadashi Toki Isao Yasumatsu Toshihiko Akimoto Kaoru Morishita Tomonori Yamasaki Takanori Yasukochi Shin Iimura 《Bioorganic & medicinal chemistry letters》2010,20(17):5113-5118
Imidazo[1,2-b]pyridazine derivatives from high-throughput screening were developed as IKKβ inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b]pyridazine scaffold, cell-free IKKβ inhibitory activity and TNFα inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure–activity relationship was revealed and the interaction model of imidazo[1,2-b]pyridazine compounds with IKKβ was constructed. 相似文献
86.
Yoshinori Takeda Naomi Tanigawa Fortunatus Sunghwa Masayuki Ninomiya Makoto Hagiwara Kenji Matsushita Mamoru Koketsu 《Bioorganic & medicinal chemistry letters》2010,20(16):4855-4857
A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell–cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC50 = 49.3 μM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC50 = 88.2 μM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-α-induced E-selectin expression. 相似文献
87.
Yoshimi Tokuzawa Ken Yagi Yzumi Yamashita Yutaka Nakachi Itoshi Nikaido Hidemasa Bono Yuichi Ninomiya Yukiko Kanesaki-Yatsuka Masumi Akita Hiromi Motegi Shigeharu Wakana Tetsuo Noda Fred Sablitzky Shigeki Arai Riki Kurokawa Toru Fukuda Takenobu Katagiri Christian Sch?nbach Tatsuo Suda Yosuke Mizuno Yasushi Okazaki 《PLoS genetics》2010,6(7)
88.
Eiji Yamamoto Tomonori Takashi Yoichi Morinaka Shaoyang Lin Jianzhong Wu Takashi Matsumoto Hidemi Kitano Makoto Matsuoka Motoyuki Ashikari 《Molecular genetics and genomics : MGG》2010,283(4):305-315
Reproductive isolation plays an important role in speciation as it restricts gene flow and accelerates genetic divergence
between formerly interbreeding population. In rice, hybrid breakdown is a common reproductive isolation observed in both intra
and inter-specific crosses. It is a type of post-zygotic reproductive isolation in which sterility and weakness are manifested
in the F2 and later generations. In this study, the physiological and molecular basis of hybrid breakdown caused by two recessive genes,
hbd2 and hbd3, in a cross between japonica variety, Koshihikari, and indica variety, Habataki, were investigated. Fine mapping of hbd2 resulted in the identification of the causal gene as casein kinase I (CKI1). Further analysis revealed that hbd2-CKI1 allele gains its deleterious function that causes the weakness phenotype by a change of one amino acid. As for the other
gene, hbd3 was mapped to the NBS-LRR gene cluster region. It is the most common class of R-gene that triggers the immune signal in response to pathogen attack. Expression analysis of pathogen response marker genes
suggested that weakness phenotype in this hybrid breakdown can be attributed to an autoimmune response. So far, this is the
first evidence linking autoimmune response to post-zygotic isolation in rice. This finding provides a new insight in understanding
the molecular and evolutionary mechanisms establishing post-zygotic isolation in plants. 相似文献
89.
Kobari Toru; Ikeda Tsutomu; Kanno Yasuji; Shiga Naonobu; Takagi Shogo; Azumaya Tomonori 《Journal of plankton research》2003,25(5):483-494
As the integral components of zooplankton in the subarctic NorthPacific, the three Neocalanus species (N. cristatus, N. plumchrusand N. flemingeri) are characterized by an annual life cycleand rapid development in the surface layer during springsummer.Patterns of interannual variation of abundance and body sizeof these Neocalanus species were analyzed using the time-seriesdata collected during the summers of 19791998 (20 years)at stations along the longitudinal transect line in the centralNorth Pacific, crossing five sub-areas (Alaska Current System,Subarctic Current System, Northern Transition Domain, SouthernTransition Domain and Subtropical Current System). In the southernsub-areas, quasi-decadal oscillation was observed for the 3-yearrunning mean of abundance and prosome length for copepoditestage 5 (C5) of the three Neocalanus species. Although the oscillationsignal diminished towards northern waters, it showed a positivephase during the early 1980s and 1990s and a negative phaseduring the late 1980s. In the northern waters, a biennial patternwas pronounced for anomalies of C5 prosome length for N. plumchrusand N. flemingeri, which was large in odd years and small ineven years. Significantly positive covariations among the threespecies were found for both abundance and prosome length aroundmid-latitude, where they were abundant. In the correlation analysis,these observed yearly patterns showed a statistically insignificantcorrelation with most environmental (integrated mean temperaturein surface waters, water column stability and chlorophyll aconcentration) or climatological (North Pacific Index and SouthernOscillation Index) variables. The regional difference of theoscillation signal and the synchronized covariation among thesespecies suggest that interannual variations of their abundanceand body size are mediated by common environmental force(s)with some spatial and temporal scales in the subarctic NorthPacific. 相似文献
90.
Furuichi K Katakura Y Ninomiya K Shioya S 《Applied and environmental microbiology》2007,73(10):3137-3143
The production of 1,4-dihydroxy-2-naphthoic acid (DHNA) was investigated using a fed-batch culture of Propionibacterium freudenreichii ET-3. DHNA is a precursor of menaquinone (MK) and is transformed to MK by combination with an isoprenoid unit. We found that ET-3 stopped MK production and increased DHNA production in an anaerobic fed-batch culture by maintaining the lactose concentration at approximately zero. The maximum DHNA concentration observed in the anaerobic fed-batch culture was markedly higher than the maximum DHNA concentration observed in an anaerobic batch culture. Moreover, MK or DHNA production was affected by the lactose feeding rate; this suggests that lactose metabolism participates in the syntheses of these products. On the other hand, accumulation of propionate was found to inhibit DHNA production in the fed-batch culture. Based on the fact that ET-3 increases DHNA production in an aerobic culture by consuming propionate, we carried out a cultivation experiment in which an anaerobic fed-batch culture was switched to an anaerobic batch culture and found that the DHNA production was increased to a greater extent than the DHNA production in an anaerobic fed-batch culture. These results suggest that DHNA production by ET-3 is markedly influenced by carbon source limitation and the oxygen supply. 相似文献