全文获取类型
收费全文 | 1410篇 |
免费 | 86篇 |
专业分类
1496篇 |
出版年
2022年 | 12篇 |
2021年 | 16篇 |
2019年 | 8篇 |
2018年 | 19篇 |
2017年 | 9篇 |
2016年 | 25篇 |
2015年 | 37篇 |
2014年 | 34篇 |
2013年 | 67篇 |
2012年 | 70篇 |
2011年 | 69篇 |
2010年 | 44篇 |
2009年 | 45篇 |
2008年 | 63篇 |
2007年 | 58篇 |
2006年 | 52篇 |
2005年 | 75篇 |
2004年 | 81篇 |
2003年 | 68篇 |
2002年 | 43篇 |
2001年 | 68篇 |
2000年 | 52篇 |
1999年 | 48篇 |
1998年 | 22篇 |
1997年 | 13篇 |
1996年 | 20篇 |
1995年 | 14篇 |
1994年 | 15篇 |
1993年 | 15篇 |
1992年 | 27篇 |
1991年 | 25篇 |
1990年 | 18篇 |
1989年 | 24篇 |
1988年 | 29篇 |
1987年 | 24篇 |
1986年 | 22篇 |
1985年 | 18篇 |
1984年 | 12篇 |
1983年 | 18篇 |
1982年 | 11篇 |
1981年 | 7篇 |
1980年 | 14篇 |
1979年 | 14篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1971年 | 9篇 |
1966年 | 5篇 |
排序方式: 共有1496条查询结果,搜索用时 0 毫秒
101.
Bacteriorhodopsin (bR) is the prototype of an integral membrane protein with seven membrane-spanning α-helices and serves as a model of the G-protein-coupled drug receptors. This study is aimed at reaching a greater understanding of the role of amine local anesthetic cations on the proton transport in the bR protein, and furthermore, the functional role of “the cation” in the proton pumping mechanism. The effect of the amine anesthetic cations on the proton pump in the bR blue membrane was compared with those by divalent (Ca2+, Mg2+ and Mn2+) and monovalent metal cations (Li+, Na+, K+ and Cs+), which are essential for the correct functioning of the proton pumping of the bR protein. The results suggest that the interacting site of the divalent cation to the bR membrane may differ from that of the monovalent metal cation. The electric current profile of the bR blue membrane in the presence of the amine anesthetic cations was biphasic, involving the generation and inhibition of the proton pumping activity in a concentration-dependent manner. The extent of the regeneration of the proton pump by the additives increased in the order of monovalent metal cation<monovalent amine anesthetic cation<divalent metal cation. We found that organic cations such as the amine anesthetics can also regenerate the proton pump in the bR protein. The inhibition of proton transport in the bR protein by the anesthetic cations was elucidated using the wild type, the E204Q and the D96N mutated bRs. The hydrophobic interaction of the amine anesthetics with the bR protein plays an important part in inhibiting the bR proton pump. 相似文献
102.
Ohmori K Umeda M Tanaka N Takagi H Yoshimura I Sasaki K Asasda S Sakai A Araki H Asakura M Baba H Fushiwaki Y Hamada S Kitou N Nakamura T Nakamura Y Oishi H Sasaki S Shimada S Tsuchiya T Uno Y Washizuka M Yajima S Yamamoto Y Yamamura E Yatsushiro T;Non-Genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan 《Alternatives to laboratory animals : ATLA》2005,33(6):619-639
The Bhas promotion assay is a cell culture transformation assay designed as a sensitive and economical method for detecting the tumour-promoting activities of chemicals. In order to validate the transferability and applicability of this assay, an inter-laboratory collaborative study was conducted with the participation of 14 laboratories. After confirmation that these laboratories could obtain positive results with two tumour promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA) and lithocholic acid (LCA), 12 coded chemicals were assayed. Each chemical was tested in four laboratories. For eight chemicals, all four laboratories obtained consistent results, and for two of the other four chemicals, only one of the four laboratories showed inconsistent results. Thus, the rate of consistency was high. During the study, several issues were raised, each of which were analysed step-by-step, leading to revision of the protocol of the original assay. Among these issues were the importance of careful maintenance of mother cultures and the adoption of test concentrations for toxic chemicals. In addition, it is suggested that three different types of chemicals show positive promoting activity in the assay. Those designated as T-type induced extreme growth enhancement, and included TPA, mezerein, PDD and insulin. LCA and okadaic acid belonged to the L-type category, in which transformed foci were induced at concentrations showing growth-inhibition. In contrast, M-type chemicals, progesterone, catechol and sodium saccharin, induced foci at concentrations with little or slight growth inhibition. The fact that different types of chemicals similarly induce transformed foci in the Bhas promotion assay may provide clues for elucidating mechanisms of tumour promotion. 相似文献
103.
Chen H Kintner DB Jones M Matsuda T Baba A Kiedrowski L Sun D 《Journal of neurochemistry》2007,102(6):1783-1795
We investigated the role of Na(+)-K(+)-Cl(-) co-transporter isoform 1 (NKCC1) and reversal of Na(+)/Ca(2+) exchanger (NCX(rev)) in glutamate-mediated excitotoxicity in oligodendrocytes obtained from rat spinal cords (postnatal day 6-8). An immunocytochemical characterization showed that these cultures express NKCC1 and Na(+)/Ca(2+) exchanger isoforms 1, 2, and 3 (NCX1, NCX2, NCX3). Exposing the cultures to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) plus cyclothiazide (CTZ) led to a transient rise in intracellular (), which was followed by a sustained overload, NKCC1 phosphorylation, and a NKCC1-mediated Na(+) influx. In the presence of a specific AMPA receptor inhibitor 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), the AMPA/CTZ failed to elicit any changes in . The AMPA/CTZ-induced sustained rise led to mitochondrial Ca(2+) accumulation, release of cytochrome c from mitochondria, and cell death. The AMPA/CTZ-elicited increase, mitochondrial damage, and cell death were significantly reduced by inhibiting NKCC1 or NCX(rev). These data suggest that in cultured oligodendrocytes, activation of AMPA receptors leads to NKCC1 phosphorylation that enhances NKCC1-mediated Na(+) influx. The latter triggers NCX(rev) and NCX(rev)-mediated overload and compromises mitochondrial function and cellular viability. 相似文献
104.
Nakano Y Kohno T Hibi T Kohno S Baba A Mikoshiba K Nakajima K Hattori M 《The Journal of biological chemistry》2007,282(28):20544-20552
Reelin is a very large secreted glycoprotein essential for correct development of the mammalian brain. It is also implicated in higher functions and diseases of human brain. However, whether or not secretion of Reelin is regulated and how Reelin transmits signals remain largely unknown. Reelin protein is composed of an N-terminal F-spondin-like domain, Reelin repeats, and a short and highly basic C-terminal region (CTR). The primary sequence of CTR is almost completely conserved among vertebrates except fishes, indicating its importance. A prevailing idea regarding the function of CTR is that it is required for the secretion of Reelin, although this remains unproven. Here we aimed to clarify the function of Reelin CTR. Neither deleting most of CTR nor replacing CTR with unrelated amino acids affected secretion efficiency, indicating that CTR is not absolutely required for the secretion of Reelin. We also found that Reelin mutants without CTR were less potent in activating the downstream signaling in cortical neurons. Although these mutants were able to bind to the Reelin receptor ectodomain as efficiently as wild-type Reelin, quite interestingly, their ability to bind to the isolated cell membrane bearing Reelin receptors or receptor-expressing cells (including cortical neurons) was much weaker than that of wild-type Reelin. Therefore, it is concluded that the CTR of Reelin is not essential for its secretion but is required for efficient activation of downstream signaling events, presumably via binding to an unidentified "co-receptor" molecule(s) on the cell membrane. 相似文献
105.
Induction of potent CD8+ T-cell responses by novel biodegradable nanoparticles carrying human immunodeficiency virus type 1 gp120 下载免费PDF全文
The mainstream of recent anti-AIDS vaccines is a prime/boost approach with multiple doses of the target DNA of human immunodeficiency virus type 1 (HIV-1) and recombinant viral vectors. In this study, we have attempted to construct an efficient protein-based vaccine using biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs), which are capable of inducing potent cellular immunity. A significant expansion of CD8+ T cells specific to the major histocompatibility complex class I-restricted gp120 epitope was observed in mice intranasally immunized once with gp120-carrying NPs but not with gp120 alone or gp120 together with the B-subunit of cholera toxin. Both the gp120-encapsulating and -immobilizing forms of NPs could induce antigen-specific spleen CD8+ T cells having a functional profile of cytotoxic T lymphocytes. Long-lived memory CD8+ T cells could also be elicited. Although a substantial decay in the effector memory T cells was observed over time in the immunized mice, the central memory T cells remained relatively constant from day 30 to day 238 after immunization. Furthermore, the memory CD8+ T cells rapidly expanded with boosting with the same immunogen. In addition, gamma-PGA NPs were found to be a much stronger inducer of antigen-specific CD8+ T-cell responses than nonbiodegradable polystyrene NPs. Thus, gamma-PGA NPs carrying various HIV-1 antigens may have great potential as a novel priming and/or boosting tool in current vaccination regimens for the induction of cellular immune responses. 相似文献
106.
N Chida-Sakata M Baba H Inagawa A Wada T Tanaka Y Hoshihara T Takemoto 《Microbiology and immunology》1999,43(5):397-401
The Etest is widely used for measuring the susceptibility of Helicobacter pylori to metronidazole. By using 55 H. pylori isolates from 55 patients and a standard H. pylori strain, NCTC11637, we compared metronidazole susceptibility results obtained from the Etest with or without anaerobic preincubation to those obtained from the agar dilution method. Mueller Hinton agar plates supplemented with 5% horse blood were used for both methods. For the Etest, plates were incubated for 72 hr at 35 C under microaerophilic conditions after 0-, 4- or 24-hr periods of anaerobic preincubation. For the agar dilution method, the plates were incubated at the same microaerophilic conditions as those for the Etest. Without anaerobic preincubation for the Etest, 39 of the 56 (70%) H. pylori isolates were categorized as resistant to metronidazole (minimal inhibitory concentration>8 mg/liter), whereas only one of the 56 (1.8%) isolates was resistant according to the agar dilution method. The resistant and susceptible agreement rate was 32%. Four-hour anaerobic preincubation did not alter the readings of the Etest significantly. However, when the Etest was performed with 24-hr anaerobic preincubation, the number of isolates categorized as resistant was reduced to six (11%), improving the agreement rate to 91%. For measuring the metronidazole susceptibility of H. pylori by the Etest, 24-hr anaerobic preincubation is necessary to agree with the results obtained by the agar dilution test. 相似文献
107.
Breaking the apple embryo dormancy by nitric oxide involves the stimulation of ethylene production 总被引:4,自引:0,他引:4
Mature seeds of apple (Mallus domestica Borb. cv. Antonówka) are dormant and do not germinate unless their dormancy is removed by several weeks of moist-cold treatment.
We investigated the effect of short-term (3 h) nitric oxide (NO) pretreatment on breaking of apple embryonic dormancy expressed
as inhibition of germination and morphological abnormalities of young seedlings. Imbibition of embryos isolated from dormant
apple seeds with sodium nitroprusside (SNP) or S-nitroso,N-acetyl penicillamine (SNAP) as NO donors resulted in enhanced germination. Moreover, NO treatment removed morphological abnormalities
of seedlings developing from dormant embryo. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-1-oxyl-3 oxide
(cPTIO) removed the above effects. NO-mediated breaking of embryonic dormancy correlated well with enhanced ethylene production.
Inhibitor of ethylene synthesis (AOA) reversed the stimulatory effect of NO donors on embryo germination. Additionally SNP
reduced embryo sensitivity to exogenously applied ABA ensuing dormancy breakage. We can conclude that NO acts as a regulatory
factor included in the control of apple embryonic dormancy breakage by stimulation of ethylene biosynthesis. 相似文献
108.
109.
Yamada T Sakisaka T Hisata S Baba T Takai Y 《The Journal of biological chemistry》2005,280(38):33026-33034
Rap1 and Rho small G proteins have been implicated in the neurite outgrowth, but the functional relationship between Rap1 and Rho in the neurite outgrowth remains to be established. Here we identified a potent Rho GTPase-activating protein (GAP), RA-RhoGAP, as a direct downstream target of Rap1 in the neurite outgrowth. RA-RhoGAP has the RA and GAP domains and showed GAP activity specific for Rho, which was enhanced by the binding of the GTP-bound active form of Rap1 to the RA domain. Overexpression of RA-RhoGAP induced inactivation of Rho for promoting the neurite outgrowth in a Rap1-dependent manner. Knockdown of RA-RhoGAP reduced the Rap1-induced neurite outgrowth. These results indicate that RA-RhoGAP transduces a signal from Rap1 to Rho and regulates the neurite outgrowth. 相似文献
110.