全文获取类型
收费全文 | 9715篇 |
免费 | 719篇 |
国内免费 | 819篇 |
出版年
2024年 | 16篇 |
2023年 | 121篇 |
2022年 | 329篇 |
2021年 | 632篇 |
2020年 | 358篇 |
2019年 | 472篇 |
2018年 | 466篇 |
2017年 | 317篇 |
2016年 | 449篇 |
2015年 | 684篇 |
2014年 | 797篇 |
2013年 | 781篇 |
2012年 | 923篇 |
2011年 | 851篇 |
2010年 | 500篇 |
2009年 | 451篇 |
2008年 | 509篇 |
2007年 | 418篇 |
2006年 | 332篇 |
2005年 | 270篇 |
2004年 | 237篇 |
2003年 | 243篇 |
2002年 | 200篇 |
2001年 | 147篇 |
2000年 | 113篇 |
1999年 | 130篇 |
1998年 | 74篇 |
1997年 | 70篇 |
1996年 | 64篇 |
1995年 | 50篇 |
1994年 | 37篇 |
1993年 | 26篇 |
1992年 | 39篇 |
1991年 | 22篇 |
1990年 | 21篇 |
1989年 | 37篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 21篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 2篇 |
1981年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 553 毫秒
161.
Yulia Zilber Sima Babayeva Jung Hwa Seo Jia Jia Liu Steven Mootin Elena Torban 《Molecular biology of the cell》2013,24(5):555-565
The planar cell polarity (PCP) pathway controls multiple cellular processes during vertebrate development. Recently the PCP pathway was implicated in ciliogenesis and in ciliary function. The primary cilium is an apically projecting solitary organelle that is generated via polarized intracellular trafficking. Because it acts as a signaling nexus, defects in ciliogenesis or cilial function cause multiple congenital anomalies in vertebrates. Loss of the PCP effector Fuzzy affects PCP signaling and formation of primary cilia; however, the mechanisms underlying these processes are largely unknown. Here we report that Fuzzy localizes to the basal body and ciliary axoneme and is essential for ciliogenesis by delivering Rab8 to the basal body and primary cilium. Fuzzy appears to control subcellular localization of the core PCP protein Dishevelled, recruiting it to Rab8-positive vesicles and to the basal body and cilium. We show that loss of Fuzzy results in inhibition of PCP signaling and hyperactivation of the canonical WNT pathway. We propose a mechanism by which Fuzzy participates in ciliogenesis and affects both canonical WNT and PCP signaling. 相似文献
162.
163.
164.
165.
166.
Previous studies have shown that evodiamine could trigger apoptosis in human malignant melanoma A375-S2 cells within 24 h. To further investigate the biochemical basis of this activity, the roles of reactive oxygen species (ROS) and mitochondrial permeability transition (MPT) were evaluated. Exposure to evodiamine led to a rapid increase in intracellular ROS followed by an onset of mitochondrial depolarization. ROS scavenger rescued the ΔΨm dissipation and cell death induced by evodiamine, whilst MPT inhibitor blocked the second-time ROS formation as well as cell death. Expressions of key proteins in Fas- and mitochondria-mediated pathways were furthermore examined. Both pathways were activated and regulated by ROS and MPT and were converged to a final common pathway involving the activation of caspase-3. These data suggested that a phenomenon termed ROS-induced ROS release (RIRR) was involved in evodiamine-treated A375-S2 cells and greatly contributed to the apoptotic process through both extrinsic and intrinsic pathways. 相似文献
167.
The redox environment of the cell is currently thought to be extremely important to control either apoptosis or autophagy. This study reported that reactive oxygen species (ROS) and nitric oxide (NO) generations were induced by evodiamine time-dependently; while they acted in synergy to trigger mitochondria-dependent apoptosis by induction of mitochondrial membrane permeabilization (MMP) through increasing the Bax/Bcl-2 or Bcl-xL ratio. Autophagy was also stimulated by evodiamine, as demonstrated by the positive autophagosome-specific dye monodansylcadaverine (MDC) staining as well as the expressions of autophagy-related proteins, Beclin 1 and LC3. Pre-treatment with 3-MA, the specific inhibitor for autophagy, dose-dependently decreased cell viability, indicating a survival function of autophagy. Importantly, autophagy was found to be promoted or inhibited by ROS/NO in response to the severity of oxidative stress. These findings could help shed light on the complex regulation of intracellular redox status on the balance of autophagy and apoptosis in anti-cancer therapies. 相似文献
168.
Juanhong Zhang Yinfu Wang Hua Xie Rong Wang Zhengping Jia Xiandong Men Liting Xu Qiang Zhang 《Cell biochemistry and biophysics》2013,65(3):363-372
New oral granules of amoxicillin and clavulanic acid in 8:1 ratio have recently been developed and approved to conduct clinical trial in China. To date, there has been no report studying the pharmacokinetic characteristics of amoxicillin and clavulanic acid in man. Therefore, it is urgent to investigate the pharmacokinetic properties of amoxicillin and clavulanic acid in man. The aim of the study was to assess the pharmacokinetic properties of amoxicillin and clavulanic acid in 8:1 with different dosage in healthy volunteers and provide support for this drug to obtain marketing authorization in China. A liquid chromatography-tandem mass spectrometry method for determining the concentration of amoxicillin and clavulanic acid in human plasma was developed and applied to this open-label, single- and multiple-dose Pharmacokinetics study. Subjects were randomized to receive a single dose of 1, 2, and 4 pouches of the test granulation of amoxicillin and clavulanic acid in 8:1 ratio (amoxicillin is 250 mg and clavulanic acid is 31.25 mg per pouch). In the single-dose phase, blood samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 12, and 24 h after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 1, 2, 3, and 4 to determine the Cmin of amoxicillin and clavulanic acid. In the 4th day, samples were collected from 0.25 to 24 h after drug administration. Profiles of the concentration–time curves of amoxicillin and clavulanic acid were best fitted to two-compartment model. In this group of healthy Chinese subjects, the pharmacokinetics of amoxicillin fitted the linear dynamic feature at doses of 250,500 and 1,000 mg, and not obviously about clavulanic acid at doses of 31.25, 62.5, and 125 mg. The t 1/2 of single dose and multidoses were (1.45 ± 0.12) and (1.44 ± 0.26) h of amoxicillin and (1.24 ± 0.23) and (1.24 ± 0.17) of clavulanic acid, respectively; The AUC0–24 of single dose and multidoses were (27937.85 ± 4265.59) and (24569.80 ± 3663.63) ng h mL?1 of amoxicillin and (891.45 ± 194.30) and (679.61 ± 284.05) ng h mL?1 of clavulanic acid, respectively; The Cmax of single dose and multidoses were (8414.58 ± 1416.78) and (7929.17 ± 1291.54) ng mL?1 of amoxicillin and (349.00 ± 89.54) and (289.00 ± 67.36) ng h mL?1 of clavulanic acid, respectively. t 1/2, AUC0–24, and Cmax were similar after multiple-dose administration and after single-dose administration, suggesting that amoxicillin and clavulanic acid do not accumulate with multiple-dose administration of 500 and 62.5 mg, respectively. 相似文献
169.
Wei Jin Kuntong Jia Lili Yang Jialin Chen Yuping Wu Meisheng Yi 《In vitro cellular & developmental biology. Animal》2013,49(6):449-457
The marine mammalian Indo-Pacific humpback dolphin, once widely lived in waters of the Indian to western Pacific oceans, has become an endangered species. The individual number of this dolphin has significantly declined in recent decades, which raises the concern of extinction. Direct concentration on laboratorial conservation of the genetic and cell resources should be paid to this marine species. Here, we report the successful derivation of cell lines form the skin of Indo-Pacific humpback dolphin. The cell cultures displayed the characteristics of fibroblast in morphology and grew rapidly at early passages, but showed obvious growth arrest at higher passages. The karyotype of the cells consisted of 42 autosomes and sex chromosomes X and Y. The immortalized cell lines obtained by forced expression of the SV40 large T-antigen were capable of proliferation at high rate in long-term culture. Immortalization and long-term culture did not cause cytogenetically observable abnormality in the karyotype. The cell type of the primary cultures and immortalized cell lines were further characterized as fibroblasts by the specific expression of vimentin. Gene transfer experiments showed that exogenetic genes could be efficiently delivered into the cells by both plasmid transfection and lentivirus infection. The cells derived from the skin of the Indo-Pacific humpback dolphin may serve as a useful in vitro system for studies on the effects of environmental pollutants and pathogens in habitats on the dolphin animals. More importantly, because of their high proliferation rate and susceptibility to lentivirus, these cells are potential ideal materials for generation of induced pluripotent stem cells. 相似文献
170.
Meina Wang Erik R Sampson Hongting Jin Jia Li Qiao H Ke Hee-Jeong Im Di Chen 《Arthritis research & therapy》2013,15(1):R5