全文获取类型
收费全文 | 21581篇 |
免费 | 1849篇 |
国内免费 | 2212篇 |
出版年
2024年 | 43篇 |
2023年 | 249篇 |
2022年 | 611篇 |
2021年 | 1184篇 |
2020年 | 756篇 |
2019年 | 957篇 |
2018年 | 960篇 |
2017年 | 783篇 |
2016年 | 906篇 |
2015年 | 1316篇 |
2014年 | 1588篇 |
2013年 | 1748篇 |
2012年 | 2042篇 |
2011年 | 1807篇 |
2010年 | 1161篇 |
2009年 | 1020篇 |
2008年 | 1147篇 |
2007年 | 979篇 |
2006年 | 910篇 |
2005年 | 786篇 |
2004年 | 701篇 |
2003年 | 579篇 |
2002年 | 586篇 |
2001年 | 448篇 |
2000年 | 386篇 |
1999年 | 354篇 |
1998年 | 236篇 |
1997年 | 206篇 |
1996年 | 189篇 |
1995年 | 164篇 |
1994年 | 176篇 |
1993年 | 119篇 |
1992年 | 112篇 |
1991年 | 80篇 |
1990年 | 75篇 |
1989年 | 63篇 |
1988年 | 61篇 |
1987年 | 38篇 |
1986年 | 33篇 |
1985年 | 23篇 |
1984年 | 24篇 |
1983年 | 13篇 |
1982年 | 13篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1933年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 250 毫秒
1.
Yunfan Sun Liang Wu Yu Zhong Kaiqian Zhou Yong Hou Zifei Wang Zefan Zhang Jiarui Xie Chunqing Wang Dandan Chen Yaling Huang Xiaochan Wei Yinghong Shi Zhikun Zhao Yuehua Li Ziwei Guo Qichao Yu Liqin Xu Jia Fan 《Cell》2021,184(2):404-421.e16
- Download : Download high-res image (233KB)
- Download : Download full-size image
2.
Ba(2+) current through the L-type Ca(2+) channel inactivates essentially by voltage-dependent mechanisms with fast and slow kinetics. Here we found that slow inactivation is mediated by an annular determinant composed of hydrophobic amino acids located near the cytoplasmic ends of transmembrane segments S6 of each repeat of the alpha(1C) subunit. We have determined the molecular requirements that completely obstruct slow inactivation. Critical interventions include simultaneous substitution of A752T in IIS6, V1165T in IIIS6, and I1475T in IVS6, each preventing in additive manner a considerable fraction of Ba(2+) current from inactivation. In addition, it requires the S405I mutation in segment IS6. The fractional inhibition of slow inactivation in tested mutants caused an acceleration of fast inactivation, suggesting that fast and slow inactivation mechanisms are linked. The channel lacking slow inactivation showed approximately 45% of the sustained Ba(2+) or Ca(2+) current with no indication of decay. The remaining fraction of the current was inactivated with a single-exponential decay (pi(f) approximately 10 ms), completely recovered from inactivation within 100 ms and did not exhibit Ca(2+)-dependent inactivation properties. No voltage-dependent characteristics were significantly changed, consistent with the C-type inactivation model suggesting constriction of the pore as the main mechanism possibly targeted by Ca(2+) sensors of inactivation. 相似文献
3.
Xiaozhong Huang Yujuan Shi Hongjin Chen Rongrong Le Xiaohua Gong Ke Xu Qihan Zhu Feixia Shen Zimiao Chen Xuemei Gu Xiaojun Chen Xiong Chen 《Cell death & disease》2020,11(12)
Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.Subject terms: Pharmacology, Molecular biology 相似文献
4.
5.
Semiparametric Regression in Size-Biased Sampling 总被引:1,自引:0,他引:1
Ying Qing Chen 《Biometrics》2010,66(1):149-158
Summary . Size-biased sampling arises when a positive-valued outcome variable is sampled with selection probability proportional to its size. In this article, we propose a semiparametric linear regression model to analyze size-biased outcomes. In our proposed model, the regression parameters of covariates are of major interest, while the distribution of random errors is unspecified. Under the proposed model, we discover that regression parameters are invariant regardless of size-biased sampling. Following this invariance property, we develop a simple estimation procedure for inferences. Our proposed methods are evaluated in simulation studies and applied to two real data analyses. 相似文献
6.
7.
8.
9.
In tumor metastasis, the margination and adhesion of tumor cells are two critical and closely related steps, which may determine the destination where the tumor cells extravasate to. We performed a direct three-dimensional simulation on the behaviors of the tumor cells in a real microvascular network, by a hybrid method of the smoothed dissipative particle dynamics and immersed boundary method (SDPD-IBM). The tumor cells are found to adhere at the microvascular bifurcations more frequently, and there is a positive correlation between the adhesion of the tumor cells and the wall-directed force from the surrounding red blood cells (RBCs). The larger the wall-directed force is, the closer the tumor cells are marginated towards the wall, and the higher the probability of adhesion behavior happen is. A relatively low or high hematocrit can help to prevent the adhesion of tumor cells, and similarly, increasing the shear rate of blood flow can serve the same purpose. These results suggest that the tumor cells may be more likely to extravasate at the microvascular bifurcations if the blood flow is slow and the hematocrit is moderate. 相似文献
10.
Hailong Jin Congran Li Ding Li Ming Cai Zhouli Li Shuang Wang Xin Hong Bingyi Shi 《Cell biochemistry and biophysics》2013,67(3):1067-1074
Immunotoxins with selective cytotoxicity are frequently used as therapeutic immunosuppressive agents in solid-organ transplantation because of their efficiency and high specificity. In this study, we present a new recombinant immunotoxin termed anti-CTLA-4-scFv–melittin prepared from Escherichia coli aimed at clearing activated T cells at the same time avoiding all-round decline in systematic immunity. This fusion protein is composed of anti-CTLA-4-scFv unit and melittin analog unit with properties of low immunogenicity and selective cytotoxicity to CTLA-4-positive T cells. In preliminary biological activity assays, our results confirmed the feasibility of activated T cell clearance strategy and there were significant differences in cell survival rates between CTLA-4-positive group and control group at all experimental concentrations of the immunotoxin. The selective cytotoxicity, low immunogenicity, and low production cost make it an attractive alternate to traditional immunosuppressants. 相似文献