全文获取类型
收费全文 | 9764篇 |
免费 | 715篇 |
国内免费 | 828篇 |
出版年
2024年 | 14篇 |
2023年 | 124篇 |
2022年 | 330篇 |
2021年 | 642篇 |
2020年 | 359篇 |
2019年 | 475篇 |
2018年 | 472篇 |
2017年 | 320篇 |
2016年 | 452篇 |
2015年 | 696篇 |
2014年 | 799篇 |
2013年 | 786篇 |
2012年 | 932篇 |
2011年 | 857篇 |
2010年 | 499篇 |
2009年 | 451篇 |
2008年 | 504篇 |
2007年 | 420篇 |
2006年 | 328篇 |
2005年 | 270篇 |
2004年 | 238篇 |
2003年 | 242篇 |
2002年 | 201篇 |
2001年 | 147篇 |
2000年 | 113篇 |
1999年 | 129篇 |
1998年 | 74篇 |
1997年 | 68篇 |
1996年 | 64篇 |
1995年 | 51篇 |
1994年 | 36篇 |
1993年 | 25篇 |
1992年 | 39篇 |
1991年 | 22篇 |
1990年 | 21篇 |
1989年 | 37篇 |
1988年 | 16篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 21篇 |
1984年 | 4篇 |
1983年 | 8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 640 毫秒
161.
HLA-A, -B, -C, -DRB1 and -DQB1 alleles associated with different hematological diseases in Chinese population
下载免费PDF全文
![点击此处可从《Blood and Genomics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lijun Wang Dongmei Li Jie Wang Yuanyuan Jing Zhongmei Wang Yanjun Jia 《Blood and Genomics》2021,5(2):113-120
The purpose of this study was to explore the association between human leukocyte antigens (HLA)-A, -B, -C, -DRB1 and -DQB1 allele polymorphisms and different hematological diseases in Chinese groups. Retrospective analyses of HLA genotyping data in high-resolution for patients with acute myeloid leukemia (AML, 766 cases), chronic myeloid leukemia (CML, 330 cases), acute lymphoblastic leukemia (ALL, 605 cases), aplastic anemia (AA, 229 cases), myelodysplastic syndrome (MDS, 204 cases) were performed, and the susceptible or protective HLA alleles of the above-mentioned diseases were analyzed by Chi-square test and Fisher exact test with unrelated hematopoietic stem cell donors as control. The Results indicated that A*0201, B*4402, C*0701, DRB1*1201, DRB1*1401, and DQB1*0602 might be susceptible genes of AML, while A*1101, A*3303, B*5801, C*0302, DRB1*0301, DQB1*0201 and DQB1*0502 might be protective genes of AML. A*3303 might be a protective gene of CML, and DRB1*1401 might be a susceptible gene of CML. ALL's susceptible genes included A*0201, A*0210, B*5201, DRB1*1201, DRB1*1401 and DQB1*0602, but its protective genes included DQB1*0502. For AA, A*0201, A*0206, B*1511, DRB1*0901, DRB1*1401, DQB1*0303, DQB1*0602 might be susceptible genes, while A*3303, B*5801, C*0302, DRB1*1602 and DQB1*0502 might be protective genes. A*0201, A*0206, B*1511, DRB1*0901, DRB1*1401, DQB1*0303. A*0201, B*1558, B*4801, B*5201, DRB1*1401, DRB1*1501, and DQB1*0602 might be susceptible genes of MDS, and A*3303, B*4601, B*5801, C*0302, and DRB1*0901 might be protective genes of MDS. On the basis of HLA high-resolution genotyping for the first time, this study comprehensively analyzed HLA alleles associated with different hematological diseases in the Chinese population, which should provide clues for further study on the pathogenesis of these diseases. 相似文献
162.
163.
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
164.
165.
166.
167.
168.
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
169.
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
170.
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