全文获取类型
收费全文 | 3293篇 |
免费 | 184篇 |
专业分类
3477篇 |
出版年
2022年 | 13篇 |
2021年 | 24篇 |
2019年 | 21篇 |
2018年 | 40篇 |
2017年 | 44篇 |
2016年 | 58篇 |
2015年 | 87篇 |
2014年 | 85篇 |
2013年 | 253篇 |
2012年 | 158篇 |
2011年 | 172篇 |
2010年 | 98篇 |
2009年 | 96篇 |
2008年 | 173篇 |
2007年 | 188篇 |
2006年 | 166篇 |
2005年 | 161篇 |
2004年 | 152篇 |
2003年 | 173篇 |
2002年 | 175篇 |
2001年 | 71篇 |
2000年 | 89篇 |
1999年 | 80篇 |
1998年 | 47篇 |
1997年 | 40篇 |
1996年 | 30篇 |
1995年 | 39篇 |
1994年 | 22篇 |
1993年 | 39篇 |
1992年 | 64篇 |
1991年 | 42篇 |
1990年 | 35篇 |
1989年 | 48篇 |
1988年 | 34篇 |
1987年 | 37篇 |
1986年 | 40篇 |
1985年 | 38篇 |
1984年 | 38篇 |
1983年 | 26篇 |
1982年 | 16篇 |
1981年 | 24篇 |
1980年 | 28篇 |
1979年 | 21篇 |
1978年 | 15篇 |
1977年 | 24篇 |
1976年 | 20篇 |
1975年 | 21篇 |
1974年 | 20篇 |
1973年 | 15篇 |
1972年 | 15篇 |
排序方式: 共有3477条查询结果,搜索用时 15 毫秒
91.
92.
Yukioka F Matsuzaki S Kawamoto K Koyama Y Hitomi J Katayama T Tohyama M 《Neurochemistry international》2008,52(4-5):683-687
In the previous reports, we showed that the familial Alzheimer's disease (AD)-linked presenilin-1 (PS1) mutation induced the fragility to the endoplasmic reticulum (ER) stress and that caspase-4 mediates ER stress-induced- and beta-amyloid induced-apoptotic signaling in human cells. These results suggest the involvement of ER stress and caspase-4 in the cell death observed in AD. In this report, we studied the activation of caspase-4 in the familial AD-linked PS1 mutation (DeltaE9). Cleavage of caspase-4 under ER stress was enhanced by the overexpression of the familial AD-linked mutation (DeltaE9), showing that caspase-4 is a key caspase involved in the apoptotic signaling of AD. We also showed that the overexpression of caspase-4 induced cleavage of caspase-9 and caspase-3 without releasing cytochrome-c from the mitochondria. Thus, caspase-4 activates downstream caspases independently of mitochondrial apoptotic signaling and this might contribute to the pathogenesis of AD. To sum up our data, the familial AD-linked PS1 mutation accelerates the cleavage of caspase-4 under the ER stress and results in the activation of caspase-9 and caspase-3, apoptosis signal, without releasing cytochrome-c. 相似文献
93.
Ismail AB Yoshinobu T Iwasaki H Sugihara H Yukimasa T Hirata I Iwata H 《Biosensors & bioelectronics》2003,18(12):1509-1514
This article reports an investigation on light-addressable potentiometric sensor (LAPS) to be used as a possible biological cell-semiconductor hybrid that will enable us to make an interface between the physical and biological system. To increase the surface potential sensitivity, we used a LAPS structure with single insulator (SiO2) coated with poly-L-ornithine and laminin (PLOL) on Si. Efficient culturing of PC-12 and nerve cells of Lymnaea stagnalis on PLOL-coated Si3N4 and SiO2 was achieved. The thickness of the PLOL layer was found to be about 4 nm by the atomic force microscope (AFM) measurement. Using the advantage of this thin layer of PLOL, we compared the performance of a novel structure to the previously reported "PLOL-coated Si3N4/SiO2/Si" structure. Due to high insulating capacitance, the photocurrent response of the novel LAPS was found to be very steep. As a result, higher sensitivity was achieved. This steepness did not degrade during 10 days when the sensor surface was kept in contact with the cell culture medium and environment. The thickness of PLOL layer, its ability to improve the biological cell adhesion, enhanced sensitivity, and experiment with simulated neural action potential (AP) applied to the novel LAPS show a good promise for LAPS to be a biological cell-semiconductor hybrid. 相似文献
94.
Fmoc-protected Phe-Gly-type (Z)-alkene dipeptide isostere (ADI) and (E)-fluoroalkene dipeptide isostere (FADI) were synthesized and applied to Fmoc-based solid-phase peptide synthesis (SPPS). These cis-peptide bond mimetics were introduced into a bioactive pentapeptide [H-Amb-Phe-Gly-Leu-Arg-Trp-NH(2); Amb = 4-(aminomethyl) benzoic acid], which has potent GPR54 agonistic activity. The resulting pentapeptide derivatives showed low GPR54 agonistic activity, as compared with the parent peptide and (E)-ADI-containing derivative. This suggests that the trans-amide conformer of Phe-Gly peptide bond of the parent peptide would be significantly important for bioactivity. Contrary to our expectations, a (Z)-FADI-containing derivative exhibited essentially no activity, revealing the necessity of critical validation of FADI-bioisosterism. 相似文献
95.
M. Takata S. Hayashi C. E. Thomas S. Koyama T. Satoh H. Fugo 《Journal of evolutionary biology》2014,27(9):1830-1836
Life history theory predicts that natural selection favours parents who balance investment across offspring to maximize fitness. Theoretical studies have shown that the optimal level of parental investment from the offspring's perspective exceeds that of its parents, and the disparity between the two generates evolutionary conflict for the allocation of parental investment. In various species, the offspring hatch asynchronously. The age hierarchy of the offspring usually establishes competitive asymmetries within the brood and determines the allocation of parental investment among offspring. However, it is not clear whether the allocation of parental investment determined by hatching pattern is optimal for parent or offspring. Here, we manipulated the hatching pattern of the burying beetle Nicrophorus quadripunctatus to demonstrate the influence of hatching pattern on the allocation of parental investment. We found that the total weight of a brood was largest in the group that mimicked the natural hatching pattern, with the offspring skewed towards early hatchers. This increases parental fitness. However, hatching patterns with more later hatchers had heavier individual offspring weights, which increases offspring fitness, but this hatching pattern is not observed in the wild. Thus, our study suggests that the natural hatching pattern optimizes parental fitness, rather than offspring fitness. 相似文献
96.
97.
We have investigated the limited proteolysis of the third component of complement, C3, by a human leukocyte protease, cathepsin G, by using a chemically modified C3, which was prepared by treatment of C3 with methylamine and a fluorescent thiol reagent, N-(dimethylamino-4-methylcoumarinyl)-maleimide (DACM) and was thus named DACM-C3me. Although native C3 was hardly cleaved by cathepsin G, DACM-C3me was cleaved by cathepsin G into three major fragments, which were termed C3c-G (150,000 daltons, 150 kd), C3d-G (25 kd), and C3a-G (10 kd). C3c-G was composed of four disulfide-linked polypeptide chains of 75 kd, 35 kd, and two 25 kd. C3d-G and C3a-G were single-chain fragments derived from the alpha chain. The N-terminal sequence of C3d-G was determined as Thr-Glu-Asp-Ala-Val-, suggesting that cathepsin G released C3d-G by cleaving a Met-Thr peptide bond which is located at 19 residues toward the N-terminal from the cysteinyl residue forming an internal thiolester linkage in native C3. C3d-G, like C3d-K (a C3d fragment produced by the action of plasma kallikrein), was found to have bioactivities such as leukocytosis-inducing and immunosuppressive activities. 相似文献
98.
A new parameter expressing the complexity of cell shape defined as (periphery)2/(area) in 2D projection was found useful for a quantitative analysis of changes in the cell shape of Amoeba proteus and potentially of any amoeboid cells. During locomotion the complexity and the motive force of the protoplasmic streaming in amoeba varied periodically, and the Fourier analysis of the two showed a similar pattern in the power spectrum, giving a rather broad peak at about 2.5 × 10−3 Hz. The complexity increased mainly due to elongation of the cell as external Ca2+ increased. This effect was blocked by La3+, half the inhibition being attained at 1/200 amount of the coexisting Ca2+. On the other hand, the complexity decreased due to rounding up of the cell as the concentration of other cations, such as Sr2+, Mg2+, Co2+, Ni2+, Na+, K+ etc., increased. Irrespective of the opposite effects of Ca2+ and other cations on the cell shape, the ATP concentration in amoeba decreased in both cases with increase of all these cations. The irregularity in amoeboid motility is discussed in terms of a dynamic system theory. 相似文献
99.
Iwao Koyama Haruo Yamagami Toyoyasu Kuwae Munetsugu Kurata 《Prostaglandins & other lipid mediators》1982,23(6):777-785
The release of 6-keto-prostaglandin F1α (6KF1α)_and of thromboxane B2 (TXB2) from cells were investigated using mouse peritoneal exudate cells (PECs) and non-cultured peritoneal macrophages. They were prepared by adhesion to glass dishes and incubated for 1 hr at 37°C in 5% Co2 in air. Both the percentage of spreading macrophages and the release of 6KF1α and TXb2 increased in proportion to the incubation time. 6KF1α and TXB2 were released from the macrophages, not from the non-adherent cells. When PECs were incubated in silicon-coated glass dishes, the spreading of macrophages was hardly detected and lower amounts of 6KF1α and TXB2 were released from these cells compared with cells incubated in non-treated glass dishes. These findings suggest that adhesion with the correlated spreading of macrophages on glass dishes serve as a considerable physical factor for the release of 6KF1α and TXB2. 相似文献
100.
Kanavillil Nandakumar Hideki Obika Tatsuya Shinozaki Toshihiko Ooie Akihiro Utsumi Tetsuo Yano 《Biofouling》2013,29(2):123-127
The impact of pulsed laser irradiation on the marine biofilm forming bacterium Pseudoalteromonas carrageenovora was investigated in the laboratory by monitoring mortality and the post-irradiation growth pattern. The impact of laser irradiation on bacterial mortality increased with the duration of irradiation. Laser irradiation at 532 nm (0.1 J cm m 2 ) for 15 min resulted in a 53% cell mortality immediately after irradiation. However, the impact after a period of 5 h (delayed impact) was more severe. The growth pattern of irradiated samples showed a prolonged lag phase compared to the reference, due to a reduction in total viable counts (TVC) in the irradiated samples. Nucleic acid staining is suggested to be a promising technique for monitoring laser inflicted bacterial mortality. Thus, the results suggest that laser irradiation could be considered as an alternative technique to reduce the number of biofilm forming bacteria and thereby biofilm formation on hard surfaces. 相似文献