全文获取类型
收费全文 | 9177篇 |
免费 | 756篇 |
国内免费 | 929篇 |
专业分类
10862篇 |
出版年
2024年 | 40篇 |
2023年 | 172篇 |
2022年 | 376篇 |
2021年 | 617篇 |
2020年 | 413篇 |
2019年 | 460篇 |
2018年 | 448篇 |
2017年 | 340篇 |
2016年 | 427篇 |
2015年 | 602篇 |
2014年 | 711篇 |
2013年 | 721篇 |
2012年 | 904篇 |
2011年 | 781篇 |
2010年 | 490篇 |
2009年 | 419篇 |
2008年 | 449篇 |
2007年 | 391篇 |
2006年 | 334篇 |
2005年 | 274篇 |
2004年 | 221篇 |
2003年 | 183篇 |
2002年 | 152篇 |
2001年 | 106篇 |
2000年 | 112篇 |
1999年 | 105篇 |
1998年 | 84篇 |
1997年 | 85篇 |
1996年 | 56篇 |
1995年 | 57篇 |
1994年 | 71篇 |
1993年 | 34篇 |
1992年 | 39篇 |
1991年 | 33篇 |
1990年 | 25篇 |
1989年 | 31篇 |
1988年 | 16篇 |
1987年 | 15篇 |
1986年 | 10篇 |
1985年 | 20篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
Wenjuan Dong Heather Mead Lei Tian Jun-Gyu Park Juan I. Garcia Sierra Jaramillo Tasha Barr Daniel S. Kollath Vanessa K. Coyne Nathan E. Stone Ashley Jones Jianying Zhang Aimin Li Li-Shu Wang Martha Milanes-Yearsley Jordi B. Torrelles Luis Martinez-Sobrido Paul S. Keim Bridget Marie Barker Michael A. Caligiuri Jianhua Yu 《Journal of virology》2022,96(1)
62.
The use of transgenic livestock is providing new methods for obtaining pharmaceutically useful proteins. However, the protein expression profiles of the transgenic animals, including expression of milk fat globule membrane (MFGM) proteins, have not been well characterized. In this study, we compared the MFGM protein expression profile of the colostrum and mature milk from three lines of transgenic cloned (TC) cattle, i.e., expressing recombinant human α-lactalbumin (TC-LA), lactoferrin (TC-LF) or lysozyme (TC-LZ) in the mammary gland, with those from cloned non-transgenic (C) and conventionally bred normal animals (N). We identified 1, 225 proteins in milk MFGM, 166 of which were specifically expressed only in the TC-LA group, 265 only in the TC-LF group, and 184 only in the TC-LZ group. There were 43 proteins expressed only in the transgenic cloned animals, but the concentrations of these proteins were below the detection limit of silver staining. Functional analysis also showed that the 43 proteins had no obvious influence on the bovine mammary gland. Quantitative comparison revealed that MFGM proteins were up- or down-regulated more than twofold in the TC and C groups compared to N group: 126 in colostrum and 77 in mature milk of the TC-LA group; 157 in colostrum and 222 in mature milk of the TC-LF group; 49 in colostrum and 98 in mature milk of the TC-LZ group; 98 in colostrum and 132 in mature milk in the C group. These up- and down-regulated proteins in the transgenic animals were not associated with a particular biological function or pathway, which appears that expression of certain exogenous proteins has no general deleterious effects on the cattle mammary gland. 相似文献
63.
XF Wang XT Tian E Ohkoshi B Qin YN Liu PC Wu MJ Hour HY Hung K Qian R Huang KF Bastow WP Janzen J Jin SL Morris-Natschke KH Lee L Xie 《Bioorganic & medicinal chemistry letters》2012,22(19):6224-6228
Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino-3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI(50) values ranging from 0.33 to 3.45μM. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC(50) values of 2.2-3.0μM. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase. 相似文献
64.
Background
Due to shared transmission routes, hepatitis C virus (HCV) infection is highly prevalent among people infected with human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is associated with hepatotoxicity, leading to the negative effects on patients with HIV/HCV co-infection. In order to provide valuable information for HCV management in this particular population, we investigated the HCV genotypes in HIV-infected individuals from Henan and Guangxi, the two provinces with the most HIV-infected cases in China.Methods
Individuals, who acquired HIV infection through various risk routes, were recruited from Henan and Guangxi. Test of antibodies against HCV (anti-HCV) was conducted, and detection of HCV RNA was performed by PCR amplification. HCV subtypes were determined by direct sequencing of amplicons, followed by phylogenetic analysis.Results
We recruited a total of 1,112 HIV-infected people in this present study. Anti-HCV was detected from 218 (50.1%) patients from Henan and 81 (12.0%) patients from Guangxi, respectively. The highest prevalence of HIV/HCV co-infection was observed from FBDs (former blood donors) (87.2%) in Henan and IDUs (intravenous drug users) (81.8%) in Guangxi, respectively. The seroprevalence rate of HCV among people with sexual contact was significantly higher in Henan than in Guangxi (18.7% vs. 3.5%, P<0.05). The positive rate of HCV RNA in Henan and Guangxi was 30.6% (133/435) and 11.2% (76/677), respectively. Moreover, we found that 20 anti-HCV negative samples were HCV positive by PCR amplification. HCV subtype 1b (52.7%) was predominant in Henan, followed by subtype 2a (41.9%). The most frequently detected subtypes in Guangxi were 6a (35.6%) and 3b (32.9%).Conclusion
The HCV genotype distributions were different in HIV-infected people from Henan and Guangxi. HIV/HCV co-infection was not only linked to the transmission routes, but also associated with the geographic position. 相似文献65.
66.
Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H2O2) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS‐metabolizing enzymes. The superoxide anion () is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H2O2 is more abundant in the differentiating peripheral zone to promote stem cell differentiation. Moreover, H2O2 negatively regulates biosynthesis in stem cells, and increasing H2O2 levels or scavenging leads to the termination of stem cells. Our results provide a mechanistic framework for ROS‐mediated control of plant stem cell fate and demonstrate that the balance between and H2O2 is key to stem cell maintenance and differentiation. 相似文献
67.
Li Wang Yun Xiao Yanyan Ping Jing Li Hongying Zhao Feng Li Jing Hu Hongyi Zhang Yulan Deng Jiawei Tian Xia Li 《PloS one》2014,9(8)
Cross-talk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal pathways are not limited to single molecular level. Therefore, we proposed a strategy that integrates a large number of biological sources at multiple levels for systematic identification of cross-talk among risk pathways in cancer by random walk on protein interaction network. We applied the method to multi-Omics breast cancer data from The Cancer Genome Atlas (TCGA), including somatic mutation, DNA copy number, DNA methylation and gene expression profiles. We identified close cross-talk among many known cancer-related pathways with complex change patterns. Furthermore, we identified key genes (linkers) bridging these cross-talks and showed that these genes carried out consistent biological functions with the linked cross-talking pathways. Through identification of leader genes in each pathway, the architecture of cross-talking pathways was built. Notably, we observed that linkers cooperated with leaders to form the fundamentation of cross-talk of pathways which play core roles in deterioration of breast cancer. As an example, we observed that KRAS showed a direct connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub. In summary, we offer an effective way to characterize complex cross-talk among disease pathways, which can be applied to other diseases and provide useful information for the treatment of cancer. 相似文献
68.
69.
Rong Xu QingFeng Han TongYing Zhu Yeping Ren JiangHua Chen HuiPing Zhao MengHua Chen Jie Dong Yue Wang ChuanMing Hao Rui Zhang Xiaohui Zhang Mei Wang Na Tian HaiYan Wang 《PloS one》2013,8(11)
Background
Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients.Methods
Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions.Results
Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared.Conclusion
Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD. 相似文献70.
Composition and dynamics of microbial community in a zeolite biofilter-membrane bioreactor treating coking wastewater 总被引:4,自引:0,他引:4
Xiaobiao Zhu Jinping Tian Cong Liu Lujun Chen 《Applied microbiology and biotechnology》2013,97(19):8767-8775
In this study, a lab-scale anaerobic/anoxic/zeolite biofilter-membrane bioreactor (A1/A2/ZB-MBR) was designed to treat coking wastewater. The 454 pyrosequencing was used to obtain the composition and dynamics of microbial community about the treatment system. The results showed that the system yielded stable effluent chemical oxidation demand (158.5?±?21.8 mg/L) and ammonia (8.56?±?7.30 mg/L), but fluctuant total nitrogen (31.4–165.1 mg/L) concentrations. In addition, 66,256 16S rRNA gene sequences were obtained from A2 and ZB-MBR, and the microbial diversity and richness for five samples were determined. Although community compositions in the five samples were quite different, bacteria assigned to phylum Proteobacteria and class Flavobacteria commonly existed and dominated the microbial populations. The pyrosequencing analysis revealed that the microbial community shifted in the ZB-MBR with the presence of zeolite. Some taxa began to appear in ZB-MBR and contributed to the system performance. Additionally, Nitrosomonas and Nitrobacter gradually became the dominant ammonia-oxidizing bacteria and nitrite-oxidizing bacteria during the operation, respectively, which are favorable for the stabilized ammonia removal. Our results proved that the ZB-MBR is an alternative technique for treating coking wastewater. 相似文献