全文获取类型
收费全文 | 830篇 |
免费 | 33篇 |
出版年
2021年 | 7篇 |
2020年 | 4篇 |
2018年 | 4篇 |
2017年 | 9篇 |
2016年 | 13篇 |
2015年 | 24篇 |
2014年 | 27篇 |
2013年 | 48篇 |
2012年 | 37篇 |
2011年 | 45篇 |
2010年 | 15篇 |
2009年 | 25篇 |
2008年 | 46篇 |
2007年 | 51篇 |
2006年 | 50篇 |
2005年 | 53篇 |
2004年 | 56篇 |
2003年 | 39篇 |
2002年 | 27篇 |
2001年 | 8篇 |
2000年 | 13篇 |
1999年 | 9篇 |
1998年 | 9篇 |
1997年 | 10篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 15篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 24篇 |
1987年 | 11篇 |
1986年 | 13篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 7篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1970年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有863条查询结果,搜索用时 15 毫秒
81.
The function of bcl-2 in preventing cell death is well known, but the mechanisms whereby bcl-2 functions are not well characterized. One mechanism whereby bcl-2 is thought to function is by alleviating the effects of oxidative stress upon the cell. To examine whether Bcl-2 can protect cells against oxidative injury resulting from post-hypoxic reoxygenation (H/R), we subjected rat fibroblasts Rat-1 and their bcl-2 transfectants b5 to hypoxia (5% CO2, 95% N2) followed by reoxygenation (5% CO2, 95% air). The bcl-2 transfectants exhibited the cell viability superior to that of their parent non-transfectants upon treatment with reoxygenation after 24-, 48-, or 72-h hypoxia, but not upon normoxic serum-deprivation or upon serum-supplied hypoxic treatment alone. Thus bcl-2 transfection can prevent cell death of some types, which occurred during H/R but yet not appreciably until termination of hypoxia. The time-sequential events of H/R-induced cell death were shown to be executed via (1) reactive oxygen species (ROS) production at 1-12 h after H/R, (2) activation of caspases-1 and -3, at 1-3 h and 3-6 h after H/R, respectively, and (3) loss of mitochondrial membrane potential (DeltaPsi) at 3-12 h after H/R. These cell death-associated events were prevented entirely except caspase-1 activation by bcl-2 transfection, and were preceded by Bcl-2 upregulation which was executed as early as at 0-1 h after H/R for the bcl-2 transfectants but not their non-transfected counterpart cells. Thus upregulation of Bcl-2 proteins may play a role in prevention of H/R-induced diminishment of cell viability, but may be executed not yet during hypoxia itself and be actually operated as promptly as ready to go immediately after beginning of H/R, resulting in cytoprotection through blockage of either ROS generation, caspase-3 activation, or DeltaPsi decline. 相似文献
82.
We designed a novel type of cationic lipid, lipids with a cationic polar group in the polyamidoamine dendron, because these dendron-bearing lipids are expected to form complexes with plasmid DNA and achieve efficient transfection of cells by synergy of endosome buffering and membrane fusion with the endosome, both of which are useful for the promotion of the transfer of plasmid DNA from endosome to cytosol. Four kinds of lipids with polyamidoamine dendrons of first to fourth generations, DL-G1, DL-G2, DL-G3, and DL-G4, were synthesized. The lipid with a dendron of a higher generation exhibited greater ability to form lipoplexes with plasmid DNA, as estimated by agarose gel electrophoresis. While the DL-G1 lipoplex did not transfect CV1 cells, the lipoplexes containing the DL-G2, DL-G3, or DL-G4 could induce transfection of the cells, and their activity was elevated with increasing generation of the dendron. Addition of dioleoylphosphatidylethanolamine (DOPE), which is known to increase fusion ability of a lipid membrane, into the lipoplexes greatly enhanced their transfection activity. In addition, the comparison with DC-Chol-containing lipoplex, which is widely used as a nonviral vector, showed that the DL-G3-DOPE lipoplex exhibits more efficient transfections. These findings imply that these dendron-bearing lipids may form the basis for a novel family of cationic lipids for efficient gene delivery. 相似文献
83.
84.
Masayoshi Shinjoh Norio Sugaya Yoshio Yamaguchi Yuka Tomidokoro Shinichiro Sekiguchi Keiko Mitamura Motoko Fujino Hiroyuki Shiro Osamu Komiyama Nobuhiko Taguchi Yuji Nakata Naoko Yoshida Atsushi Narabayashi Michiko Myokai Masanori Sato Munehiro Furuichi Hiroaki Baba Hisayo Fujita Akihiro Sato Ichiro Ookawara Kenichiro Tsunematsu Makoto Yoshida Mio Kono Fumie Tanaka Chiharu Kawakami Takahisa Kimiya Takao Takahashi Satoshi Iwata Keio Pediatric Influenza Research Group 《PloS one》2015,10(8)
We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013–14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B. 相似文献
85.
86.
Tsubasa Fukue Motohide Tamura Ryo Kandori Nobuhiko Kusakabe James H. Hough Jeremy Bailey Douglas C. B. Whittet Philip W. Lucas Yasushi Nakajima Jun Hashimoto 《Origins of life and evolution of the biosphere》2010,40(3):335-346
We present a wide-field (∼6′ × 6′) and deep near-infrared (K
s
band: 2.14 μm) circular polarization image in the Orion nebula, where massive stars and many low-mass stars are forming.
Our results reveal that a high circular polarization region is spatially extended (∼0.4 pc) around the massive star-forming
region, the BN/KL nebula. However, other regions, including the linearly polarized Orion bar, show no significant circular
polarization. Most of the low-mass young stars do not show detectable extended structure in either linear or circular polarization,
in contrast to the BN/KL nebula. If our solar system formed in a massive star-forming region and was irradiated by net circularly
polarized radiation, then enantiomeric excesses could have been induced, through asymmetric photochemistry, in the parent
bodies of the meteorites and subsequently delivered to Earth. These could then have played a role in the development of biological
homochirality on Earth. 相似文献
87.
New delta-alkyllactones (DALs) with diverse side-chain lengths (184-254 Da), which are structurally different from the widespread, naturally occurring delta-lactones of higher molecular weight (348-439 Da), such as camptothecin and sultriecin, were chemically synthesized and analyzed for their carcinostatic activity. Of the DALs with 11, 12, 13, 14, or 16 carbon atoms, delta-hexadecalactone (DH16:0) was the most carcinostatic when administered to Ehrlich ascites tumor (EAT) cells at 37 degrees C for 20 h, and measured by the mitochondrial dehydrogenase-based WST-1 assay. Prolongation of the administration period to 72 h enhanced the carcinostatic activity more markedly for DH16:0 than for other DALs. The carcinostatic activity of DALs was unexpectedly augmented by increasing the number of carbon atoms, in contrast to the conventional view that carcinostatic activity is attenuated by the addition of carbon atoms to fatty acids. Intracellular accumulation of DH16:0, as analyzed by gas chromatography, was detected (1.5 Pg/cell), whereas other DALs studied were rarely found. The results indicate a close relationship between carcinostatic activity and intracellular accumulation. Invasion of human fibrosarcoma HT-1080 cells through the reconstituted basement membrane was inhibited by several DALs, even at doses as low as 5-10% of those necessary for carcinostatic activity, suggesting an invasive mechanism different from carcinostasis. The invasion-inhibitory activity was intensified by increasing the number of carbon atoms, in a manner similar to that for the carcinostatic activity. The lifespan of EAT-cell-transplanted mice was markedly prolonged with DH16:0, presumably due to excellent distribution throughout the body and tumor cells. Thus DH16:0 may be a potent anticancer agent, in term of its carcinostatic, anti-invasive, and lifespan-prolonging activities. 相似文献
88.
He PJ Hirata M Yamauchi N Hashimoto S Hattori MA 《Molecular and cellular biochemistry》2007,302(1-2):111-118
The circadian clock is responsible for the generation of circadian rhythms in hormonal secretion and metabolism. These peripheral
clocks could be reset by various cues in order to adapt to environmental variations. The ovary can be characterized as having
highly dynamic physiology regulated by gonadotropins. Here, we aimed to address the status of circadian clock in the ovary,
and to explore how gonadotropins could regulate clockwork in granulosa cells (GCs). To this end, we mainly utilized the immunohistochemistry,
RT-PCR, and real-time monitoring of gene expression methods. PER1 protein was constantly abundant across the daily cycle in
the GCs of immature ovaries. In contrast, PER1 protein level was obviously cyclic through the circadian cycle in the luteal
cells of pubertal ovaries. In addition, both FSH and LH induced Per1 expression in cultured immature and mature GCs, respectively. The promoter analysis revealed that the Per1 expression was mediated by the cAMP response element binding protein. In cultured transgenic GCs, both FSH and LH also induced
the circadian oscillation of Per2. However, the Per2 oscillation promoted by FSH quickly dampened within only one cycle, whereas the Per2 oscillation promoted by LH was persistently maintained. Collectively, these findings strongly suggest that both FSH and LH
play an important role in regulating circadian clock in the ovary; however, they might exert differential actions on the clockwork
in vivo due to each specific role within ovarian physiology. 相似文献
89.
A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family
Miyamoto Y Matsuda T Kitoh H Haga N Ohashi H Nishimura G Ikegawa S 《Human genetics》2007,121(5):625-629
Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of
the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity.
Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic
factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense
mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial
phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases. 相似文献
90.
Tsujimoto H Hara K Tsukada Y Huang CC Kawashima Y Arakaki M Okayasu H Mimura H Miwa N 《Bioorganic & medicinal chemistry letters》2007,17(17):4771-4777
This paper describes the process of encapsulating hair growing ingredients in the PLGA nanospheres by emulsion solvent diffusion method and investigates the feasibility of using the PLGA nanospheres as the DDS (Drug delivery System) carriers for delivering various hair growing ingredients to hair follicles. In-vitro and in-vivo tests were conducted to verify the performances of encapsulated PLGA nanospheres with three different hair growing ingredients. In the in-vitro tests, the scalp-pore permeability of hair growing ingredient encapsulated PLGA nanospheres (dispersed in the PBS solution) was examined using human scalp biopsies in a modified Bronaugh diffusion chamber in comparison to that of the control samples containing the hair growing ingredient in the PBS solution. Furthermore, the hair growing effect of the encapsulated PLGA nanospheres was evaluated with the C3H mice in the in-vivo tests. By observing the fluorescence intensity of the ingredients, as shown in the cross-section photographs of the human scalp biopsies, it was found that the dispersion liquids containing hair growing ingredient encapsulated PLGA nanospheres exerted a scalp-pore permeability 2.0- to 2.5-fold more marked than that of the control samples. Also, the hair growing activities were enhanced by using the encapsulated PLGA nanospheres, which transformed the hair growth cycle from the resting phase to the growing phase. As a result, the degree of hair growth was improved significantly. These results suggested that the PLGA nanosphere can be a new DDS carrier for delivering hair growing ingredients and drugs to the hair follicles. 相似文献