全文获取类型
收费全文 | 958篇 |
免费 | 88篇 |
出版年
2022年 | 8篇 |
2021年 | 16篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 14篇 |
2017年 | 12篇 |
2016年 | 17篇 |
2015年 | 28篇 |
2014年 | 30篇 |
2013年 | 57篇 |
2012年 | 40篇 |
2011年 | 50篇 |
2010年 | 29篇 |
2009年 | 38篇 |
2008年 | 54篇 |
2007年 | 49篇 |
2006年 | 43篇 |
2005年 | 43篇 |
2004年 | 44篇 |
2003年 | 41篇 |
2002年 | 59篇 |
2001年 | 32篇 |
2000年 | 34篇 |
1999年 | 14篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 11篇 |
1992年 | 14篇 |
1991年 | 16篇 |
1990年 | 21篇 |
1989年 | 14篇 |
1988年 | 14篇 |
1987年 | 16篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 10篇 |
1982年 | 12篇 |
1981年 | 8篇 |
1978年 | 4篇 |
1977年 | 11篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 14篇 |
1973年 | 7篇 |
1972年 | 11篇 |
1969年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有1046条查询结果,搜索用时 203 毫秒
51.
Tanida Kotomi Shimada Mihoko Khor Seik-Soon Toyoda Hiromi Kato Kayoko Kotorii Nozomu Kotorii Tatayu Ariyoshi Yu Kato Takao Hiejima Hiroshi Ozone Motohiro Uchimura Naohisa Ikegami Azusa Kume Kazuhiko Kanbayashi Takashi Imanishi Aya Kamei Yuichi Hida Akiko Wada Yamato Kuroda Kenji Miyamoto Masayuki Hirata Koichi Takami Masanori Yamada Naoto Okawa Masako Omata Naoto Kondo Hideaki Kodama Tohru Inoue Yuichi Mishima Kazuo Honda Makoto Tokunaga Katsushi Miyagawa Taku 《Sleep and biological rhythms》2022,20(1):137-148
Sleep and Biological Rhythms - Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness, great difficulty upon awakening, and prolonged sleep time. In... 相似文献
52.
Imai S Tezuka H Furuhashi Y Muto R Fujita K 《The Journal of biological chemistry》2001,276(49):46118-46124
Immune responses to parasitic helminth are usually characterized by quite mysterious phenomena: dominance of Th2-like immunity and antigen-nonspecific IgE secretion. We previously purified a factor from Dirofilaria immitis that induces antigen-nonspecific IgE in rats and named it DiAg. In the presence of IL-4, DiAg induces mouse B cells to secrete IgE, which is antigen-nonspecific polyclonal antibody. We investigated the biochemical characteristics of DiAg as a factor of inducing IgE in this study. Recombinant DiAg (rDiAg) with interleukin (IL)-4 induced IgE synthesis in highly purified human normal B cells in vitro cell culture systems. The addition of recombinant human soluble CD40 IgG fusion protein (rsCD40-Ig) inhibited induction of IgE synthesis by rDiAg with IL-4. Monocyte cells were stimulated with rDiAg and recombinant human soluble CD40L (rsCD40L); IL-12 and TNF-alpha were induced. The addition of rsCD40-Ig to THP-1 cells activated with rDiAg and rsCD40L inhibited the production of IL-12. rDiAg bound to the monocyte cell membrane fraction and recombinant human soluble CD40; this binding of rDiAg was competitively inhibited by addition of rsCD40L. Moreover, in CD40-deficient mice, IgE production and MLN-B cell proliferation by rDiAg were completely absent. Based on these results, we concluded that DiAg is an agonist of CD40. 相似文献
53.
We determined the expression and subcellular localization of nuclear protein NP95 during the cell cycle in mouse 3T3 cells. The levels of NP95 mRNA and protein were extremely low in quiescent cells; however, stimulation with 10% serum increased their expressions in a time course similar to that of the late growth-regulated gene proliferating cell nuclear antigen (PCNA). Subnuclear location of NP95 dynamically changed during the cell cycle. Double immunostaining for NP95 and chromatin-bound PCNA, a marker of DNA replication sites, revealed that NP95 was almost exclusively colocalized with chromatin-bound PCNA throughout the nucleus in early S phase and partly in mid-S phase. Distinct localization of the two proteins, however, became evident in mid-S phase, and thereafter, many chromatin-bound PCNA foci not carrying NP95 foci could be detected. In G2 phase, nodular NP95 foci were still identified without any chromatin-bound PCNA foci. Chromatin-bound PCNA was observed as a pre-DNA replication complex at the G1/S boundary synchronized by hydroxyurea treatment, while NP95 was detected in nucleolar regions as unique large foci. There was no significant redistribution of NP95 foci shortly after DNA damage by gamma-irradiation. Nodular NP95 foci characteristically seen in G2 phase were also detected in G2-arrested cells following gamma-irradiation. Taken together, our results indicate that NP95 is assigned to a late growth-regulated gene and suggest that NP95 does not take a direct part in DNA replication as part of the DNA synthesizing machinery, like PCNA, but is presumably involved in other DNA replication-linked nuclear events. 相似文献
54.
55.
Morikane K Tempero RM Sivinski CL Nomoto M Van Lith ML Muto T Hollingsworth MA 《Cancer immunology, immunotherapy : CII》1999,47(5):287-296
We established a model of orthotopic injection of a syngeneic pancreatic tumor cell line in C57BL/6 mice and evaluated the
effects of organ site on induction of immunity to a tumor-specific antigen, MUC1. Mice were challenged with a syngeneic pancreatic
adenocarcinoma cell line that expressed MUC1 (Panc02-MUC1) by orthotopic injection into the pancreas, or by subcutaneous injection.
Tumor cells injected into the pancreas grew much faster than those injected subcutaneously. Mice challenged subcutaneously
with Panc02-MUC1 rejected tumors or developed slowly growing tumors that were negative for MUC1 expression. In contrast, mice
challenged orthotopically into the pancreas developed progressive tumors that were positive for MUC1 expression. Sera from
mice that rejected Panc02-MUC1 (tumor-immune mice) showed no detectable IgG1 and IgM titers against the MUC1 tandem-repeat
peptide, whereas mice with progressive tumor growth had significant titers of IgG1 and IgM specific for MUC1. This suggests
that the humoral immune response was ineffective in mediating tumor rejection. The results show that the growth properties
and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.
Received: 25 April 1998 / Accepted: 7 October 1998 相似文献
56.
Six1 controls patterning of the mouse otic vesicle 总被引:3,自引:0,他引:3
Ozaki H Nakamura K Funahashi J Ikeda K Yamada G Tokano H Okamura HO Kitamura K Muto S Kotaki H Sudo K Horai R Iwakura Y Kawakami K 《Development (Cambridge, England)》2004,131(3):551-562
Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent. 相似文献
57.
Fujii N Nozawa T Igawa A Kato B Igarashi N Nonomura M Asanoi H Tazawa S Inoue M Inoue H 《American journal of physiology. Heart and circulatory physiology》2004,287(2):H760-H766
Abnormalities in energy metabolism may play an important role in the development of hypertensive heart failure. However, the transition from compensated hypertrophy to heart failure is not fully understood in terms of energy metabolism. In Dahl salt-sensitive (DS) and salt-resistant (DR) rats, myocardial fatty acid and glucose uptake values were determined using (131)I- or (125)I-labeled 9-methylpentadecanoic acid ((131)I- or (125)I-9MPA), and [(14)C]deoxyglucose ([(14)C]DG), fatty acid beta-oxidation was identified using thin-layer chromatography, and insulin-stimulated glucose-uptake was observed using a euglycemic hyperinsulinemic glucose clamp. Six-week-old rats were fed a diet that contained 8% NaCl, which resulted in development of compensated hypertrophy in DS rats at 12 wk of age and ultimately led to heart failure by 18 wk of age. Uptake of [(14)C]DG increased markedly with age in the DS rats, whereas (131)I-9MPA uptake was marginally but significantly increased only in animals aged 12 wk. The ratio of (125)I-9MPA beta-oxidation metabolites to total uptake in the DS rats was significantly lower (P < 0.05) at 12 (37%) and 18 (34%) wk compared with at 6 (45%) wk. Insulin increased [(14)C]DG uptake more than twofold in the DS rats at 6 wk, although this increase was markedly attenuated at 12 and 18 wk (11 and 8%, respectively). Our data suggest that in a hypertrophied heart before heart failure, fatty acid oxidation is impaired and the capacity to increase glucose uptake during insulin stimulation is markedly reduced. These changes in both glucose and fatty acid metabolism that occur in association with myocardial hypertrophy may have a pathogenic role in the subsequent development of heart failure. 相似文献
58.
Ogino H Mimitsuka T Muto T Matsumura M Yasuda M Ishimi K Ishikawa H 《Journal of molecular microbiology and biotechnology》2004,7(4):212-223
A lipolytic enzyme gene (lip8) was cloned from organic solvent-tolerant Pseudomonas aeruginosa LST-03 and sequenced. In the sequenced nucleotides, an open reading frame consisting of 1,173 nucleotides and encoding 391 amino acids was found. Lip8 is considered to belong to the family VIII of lipolytic enzymes whose serine in the consensus sequence of -Ser-Xaa-Xaa-Lys- acts as catalytic nucleophile. The gene was expressed in Escherichia coli and purified by a combination of ammonium sulfate fractionation and hydrophobic interaction and ion-exchange chromatographies to homogeneity on SDS-PAGE analysis. The optimum temperature and heat stability of Lip8 were not as high as those of Lip3 and LST-03 lipase, two other lipolytic enzymes from the same strain. Addition of glycerol to a solution containing Lip8 stabilized this enzyme. By measuring the activities against various triacylglycerols and fatty acid methyl esters having carbon chains of different lengths, Lip8 was categorized as an esterase which has higher activities against fatty acid methyl esters with short-chain fatty acids. 相似文献
59.
Cady FM Muto DN Ciabeterri G Johns A Gainey Church K Wolff DJ 《Journal of the Association of Genetic Technologists》2004,30(3):77-81
Specific genetic abnormalities are of prognostic significance for patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM); however, routine cytogenetic analysis usually provides normal results. We utilized two probe panels for interphase fluorescence in situ hybridization (FISH) studies to enhance the ability to detect genetic abnormalities in samples that were referred for routine cytogenetic studies for possible diagnoses of CLL or MM. The CLL panel consisted of probes for 11q22.3 (ATM gene), 13q14 (D13S319), the centromere of chromosome 12 (D12Z3) and 17p13.1 (P53 gene). The MM panel included probes for 14q32 (IgH gene) and/or t(11:14)(q13;q32) (BCL1/IgH), 13q14 (D13S319) and 17p13.1 (P53 gene). FISH detected clonal aberrations not identified by conventional cytogenetics in an additional 8 of 23 (35%) samples referred for possible CLL and 7 of 42 (17%) samples with possible MM. The prognostic significance of the aberrations identified ranged from favorable, to intermediate, to poor. Our studies indicate that many samples referred for routine cytogenetics testing for CLL and MM yield normal results for both conventional and FISH testing, likely due to lack of definitive diagnosis in a percentage of cases. However, FISH is more sensitive for the detection of clinically significant chromosome abnormalities and should be the testing methodology of choice for these disorders. 相似文献
60.
Yada T Muto K Azuma T Ikuta K 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2004,139(1-3):57-63
In vivo and in vitro effects of prolactin (PRL) and growth hormone (GH) on plasma levels of lysozyme and ceruloplasmin were examined in the rainbow trout (Oncorhynchus mykiss). Hypophysectomy had no effect on the plasma lysozyme level. Implantation of PRL- or GH-containing cholesterol pellets increased the lysozyme level in a dose-related manner. After hypophysectomy and sham operation, plasma ceruloplasmin was elevated above the level in intact fish, suggesting inflammation caused by the surgery. PRL or GH treatment significantly attenuated the increased level of ceruloplasmin in the operated fish. Expression of lysozyme mRNA was detected in the leucocytes isolated from the peripheral blood by RT-PCR. In vitro administration of PRL or GH showed no effect on the proliferation of isolated leucocytes or on the total protein content; however, lysozyme activity in the medium increased in a dose-related manner. These results suggest that PRL and GH directly stimulate lysozyme production without affecting the proliferation of leucocytes, and the attenuated ceruloplasmin level increased in response to inflammation. 相似文献