全文获取类型
收费全文 | 11017篇 |
免费 | 848篇 |
国内免费 | 811篇 |
出版年
2024年 | 3篇 |
2023年 | 142篇 |
2022年 | 189篇 |
2021年 | 630篇 |
2020年 | 406篇 |
2019年 | 508篇 |
2018年 | 446篇 |
2017年 | 333篇 |
2016年 | 493篇 |
2015年 | 764篇 |
2014年 | 883篇 |
2013年 | 853篇 |
2012年 | 1079篇 |
2011年 | 856篇 |
2010年 | 516篇 |
2009年 | 498篇 |
2008年 | 526篇 |
2007年 | 494篇 |
2006年 | 407篇 |
2005年 | 387篇 |
2004年 | 300篇 |
2003年 | 272篇 |
2002年 | 206篇 |
2001年 | 211篇 |
2000年 | 151篇 |
1999年 | 164篇 |
1998年 | 99篇 |
1997年 | 109篇 |
1996年 | 108篇 |
1995年 | 101篇 |
1994年 | 113篇 |
1993年 | 65篇 |
1992年 | 65篇 |
1991年 | 84篇 |
1990年 | 53篇 |
1989年 | 43篇 |
1988年 | 25篇 |
1987年 | 17篇 |
1986年 | 14篇 |
1985年 | 25篇 |
1984年 | 15篇 |
1983年 | 17篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Single Cell Transcriptome Amplification with MALBAC 总被引:1,自引:0,他引:1
2.
3.
Yufeng Qian Aashiq H. Kachroo Christopher M. Yellman Edward M. Marcotte Kenneth A. Johnson 《The Journal of biological chemistry》2014,289(9):5970-5985
Mutations in the human mitochondrial polymerase (polymerase-γ (Pol-γ)) are associated with various mitochondrial disorders, including mitochondrial DNA (mtDNA) depletion syndrome, Alpers syndrome, and progressive external opthamalplegia. To correlate biochemically quantifiable defects resulting from point mutations in Pol-γ with their physiological consequences, we created “humanized” yeast, replacing the yeast mtDNA polymerase (MIP1) with human Pol-γ. Despite differences in the replication and repair mechanism, we show that the human polymerase efficiently complements the yeast mip1 knockouts, suggesting common fundamental mechanisms of replication and conserved interactions between the human polymerase and other components of the replisome. We also examined the effects of four disease-related point mutations (S305R, H932Y, Y951N, and Y955C) and an exonuclease-deficient mutant (D198A/E200A). In haploid cells, each mutant results in rapid mtDNA depletion, increased mutation frequency, and mitochondrial dysfunction. Mutation frequencies measured in vivo equal those measured with purified enzyme in vitro. In heterozygous diploid cells, wild-type Pol-γ suppresses mutation-associated growth defects, but continuous growth eventually leads to aerobic respiration defects, reduced mtDNA content, and depolarized mitochondrial membranes. The severity of the Pol-γ mutant phenotype in heterozygous diploid humanized yeast correlates with the approximate age of disease onset and the severity of symptoms observed in humans. 相似文献
4.
5.
Marek's disease virus (MDV) ICP4, pp38, and meq genes are involved in the maintenance of transformation of MDCC-MSB1 MDV-transformed lymphoblastoid cells. 总被引:7,自引:2,他引:5 下载免费PDF全文
An antisense strategy has been used to identify genes important for the maintenance of transformation of MDCC-MSB1 (MSB1) Marek's disease virus-transformed lymphoblastoid cells. Oligodeoxynucleotides antisense to the predicted translation initiation regions of ICP4 and pp38 mRNAs inhibited proliferation of MSB1 cells but not MDCC-CU91 (CU91) reticuloendotheliosis virus-transformed cells. Control oligodeoxynucleotides having the same base composition but a different sequence did not inhibit MSB1 cell proliferation. In addition, ICP4 and pp38 antisense oligodeoxynucleotides resulted in 77- and 100-fold reductions in colony formation by MSB1 cells in soft agar, respectively. To extend and corroborate these results, a novel system based on efficiently regulated expression of eukaryotic genes by a chimeric mammalian transactivator, LAP267 (S. B. Baim, M. A. Labow, A. J. Levine, and T. Shenk, Proc. Natl. Acad. Sci. USA 88:5072-5076, 1991), was used. MSB1-derived stably transfected cell lines in which RNA antisense to Marek's disease virus ICP4, pp38, or meq could be induced by treatment of the cells with isopropyl-beta-D-thiogalactopyranoside (IPTG) were constructed. Control cell lines in which expression of ICP4 sense or pUC19 sequences could be induced by IPTG were also constructed. Induction of the cell lines indicated that ICP4 antisense RNA, but not ICP4 sense RNA or pUC19 RNA, inhibited proliferation of MSB1 cells. Induction of ICP4, meq, or pp38 antisense RNAs, but not ICP4 sense or pUC19 RNAs, had a dramatic effect on relative colony formation by MSB1 cells in soft agar. These results indicate that ICP4, pp38, and Meq are all involved in the maintenance of transformation of MSB1 cells. 相似文献
6.
7.
C. Lu Z. Xie F. Yu L. Tian X. Hao X. Wang L. Chen D. Li 《Plant biology (Stuttgart, Germany)》2020,22(4):655-667
- Mitochondrial function is critical for cell vitality in all eukaryotes including plants. Although plant mitochondria contain many proteins, few have been studied in the context of plant development and physiology.
- We used knock‐down mutant RPS9M to study its important role in male gametogenesis and seed development in Arabidopsis thaliana.
- Knock‐down of RPS9M in the rps9m‐3 mutant led to abnormal pollen development and impaired pollen tube growth. In addition, both embryo and endosperm development were affected. Phenotype analysis revealed that the rps9m‐3 mutant contained a lower amount of endosperm and nuclear proteins, and both embryo cell division and embryo pattern were affected, resulting in an abnormal and defective embryo. Lowering the level of RPS9M in rps9m‐3 affects mitochondrial ribosome biogenesis, energy metabolism and production of ROS.
- Our data revealed that RPS9M plays important roles in normal gametophyte development and seed formation, possibly by sustaining mitochondrial function.
8.
9.
Sydney X. Lu Emma De Neef James D. Thomas Erich Sabio Benoit Rousseau Mathieu Gigoux David A. Knorr Benjamin Greenbaum Yuval Elhanati Simon J. Hogg Andrew Chow Arnab Ghosh Abigail Xie Dmitriy Zamarin Daniel Cui Caroline Erickson Michael Singer Hana Cho Robert K. Bradley 《Cell》2021,184(15):4032-4047.e31
10.
Pancreatic cancer is a lethal disease with limited opportunity for resectable surgery as the first choice for cure due to its late diagnosis and early metastasis. The desmoplastic stroma and cellular genetic or epigenetic alterations of pancreatic cancer impose physical and biological barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Here, we review the current therapeutic options for pancreatic cancer, and underlying mechanisms and potential reversal of therapeutic resistance, a hallmark of this deadly disease. 相似文献