全文获取类型
收费全文 | 74274篇 |
免费 | 5780篇 |
国内免费 | 4615篇 |
出版年
2023年 | 897篇 |
2022年 | 1042篇 |
2021年 | 3736篇 |
2020年 | 2620篇 |
2019年 | 3231篇 |
2018年 | 3169篇 |
2017年 | 2302篇 |
2016年 | 3262篇 |
2015年 | 4811篇 |
2014年 | 5553篇 |
2013年 | 5999篇 |
2012年 | 7032篇 |
2011年 | 6163篇 |
2010年 | 3720篇 |
2009年 | 3337篇 |
2008年 | 3729篇 |
2007年 | 3366篇 |
2006年 | 2913篇 |
2005年 | 2386篇 |
2004年 | 1960篇 |
2003年 | 1656篇 |
2002年 | 1402篇 |
2001年 | 1229篇 |
2000年 | 1219篇 |
1999年 | 1112篇 |
1998年 | 645篇 |
1997年 | 644篇 |
1996年 | 647篇 |
1995年 | 616篇 |
1994年 | 543篇 |
1993年 | 376篇 |
1992年 | 568篇 |
1991年 | 435篇 |
1990年 | 406篇 |
1989年 | 283篇 |
1988年 | 244篇 |
1987年 | 235篇 |
1986年 | 166篇 |
1985年 | 193篇 |
1984年 | 109篇 |
1983年 | 117篇 |
1982年 | 71篇 |
1981年 | 58篇 |
1980年 | 37篇 |
1979年 | 61篇 |
1977年 | 30篇 |
1976年 | 29篇 |
1974年 | 38篇 |
1973年 | 34篇 |
1972年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
102.
103.
104.
Regulatory gene of phenylalanine biosynthesis (pheR) in Salmonella typhimurium 总被引:2,自引:1,他引:1 下载免费PDF全文
4-Fluorophenylalanine-resistant mutants of Salmonella typhimurium were isolated in which synthesis of chorismate mutase P-prephenate dehydratase (specified by pheA) was highly elevated. Transduction analysis showed that the mutation affecting pheA activity was not linked to pheA, and conjugation and merodiploid analysis indicated that it was in the 95- to 100-min region of the Salmonella chromosome. Evidence is presented for the hypothesis that the mutation responsible for constitutivity of chorismate mutase P-prephenate dehydratase occurred in pheR, a gene specifying a cytoplasmic product that affected pheA. pheR mutants were found to carry a second mutation, tyrO. The tyrO mutation acts cis to cause increased levels of the tyrosine biosynthetic enzymes 3-deoxy-d-arabinoheptulosonate 7-phosphate synthetase (tyr) and prephenate dehydrogenase, but it has no effect on regulation of pheA. 相似文献
105.
Hsi-Feng Tu Chung-Ji Liu Che-Lun Chang Pei-Wen Wang Shou-Yen Kao Cheng-Chieh Yang En-Hao Yu Shu-Chun Lin Kuo-Wei Chang 《PloS one》2012,7(12)
MicroRNAs (miRNAs) play important roles in modulating the neoplastic process of cancers including head and neck squamous cell carcinoma (HNSCC). A genetic polymorphism (rs2292832, C>T) has been recently identified in the precursor of miR-149; nevertheless its clinicopathological implications remain obscure. In this study, we showed that miR-149 is down-regulated in HNSCC compared to normal mucosa and this is associated with a poorer patient survival. In addition, HNSCC patients with the T/T genotype have more advanced tumors and a worse prognosis. Multivariate analysis indicated that patients carried the T/T genotype have a 2.81-fold (95% CI: 1.58–4.97) increased risk of nodal metastasis and 1.66-fold (95% CI: 1.05–2.60) increased risk of mortality compared to other groups. T/T genotype also predicted the worse prognosis of buccal mucosa carcinoma subset of HNSCC. In vitro analysis indicated that exogenous miR-149 expression reduces the migration of HNSCC cells. Moreover, HNSCC cell subclones carrying the pri-mir-149 sequence containing the T variant show a low processing efficacy when converting the pre-mir-149 to mature miR-149. These findings suggest that miR-149 suppresses tumor cell mobility, and that the pre-mir-149 polymorphism may affect the processing of miR-149, resulting in a change in the abundance of the mature form miRNA, which, in turn, modulates tumor progression and patient survival. 相似文献
106.
In vitro fertilization of mouse ova by spermatozoa exposed isothermally to radio-frequency radiation
Mouse spermatozoa were exposed in vitro for 1 h to 27- or 2,450-MHz CW RF radiation at SARs of 0 to 90 W/kg under isothermal (37 +/- 0.2 degrees C) conditions. Exposure at either frequency to RF radiation at SARs of 50 W/kg or greater resulted in a statistically significant reduction in the ability of irradiated sperm to fertilize mouse ova in vitro (P less than .05). Over the range of SARs there was no apparent difference in the effects of 27- vs. 2,450-MHz RF radiation. There were no readily detectable exposure effects on spermatozoan morphology, ultrastructure, or capacitation. The reduction of in vitro fertilization is attributed to a direct effect of RF radiation on spermatozoa rather than to heating. 相似文献
107.
J Theodore Phillips Edward Fox William Grainger Dianne Tuccillo Shifang Liu Aaron Deykin 《BMC neurology》2011,11(1):126
Background
The ability to self-inject in patients with multiple sclerosis (MS) has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patients' independence. However, injection anxiety, needle phobia and disease-related disability are major barriers to a patient's ability to self-administer treatment. Use of an autoinjector may improve patients' ability to self-inject. This study evaluated the safe and effective use of Avonex Pen™ (prefilled pen), a single use autoinjector, for intramuscular delivery of interferon beta-1a (IM IFNβ-1a, Avonex) in MS patients. 相似文献108.
109.
Zac Yates Kannan Gunasekaran Hongxing Zhou Zhonghua Hu Zhi Liu Randal R. Ketchem Boxu Yan 《The Journal of biological chemistry》2010,285(24):18662-18671
Hydroxyl radicals induce hinge cleavage in a human IgG1 molecule via initial radical formation at the first hinge Cys231 followed by electron transfer to the upper hinge residues. To enable engineering of a stable monoclonal antibody hinge, we investigated the role of the hinge His229 residue using structure modeling and site-directed mutagenesis. Direct involvement of His229 in the reaction mechanism is suggested by a 75–85% reduction of the hinge cleavage for variants in which His229 was substituted with either Gln, Ser, or Ala. In contrast, mutation of Lys227 to Gln, Ser, or Ala increased hinge cleavage. However, the H229S/K227S double mutant shows hinge cleavage levels similar to that of the single H229S variant, further revealing the importance of His229. Examination of the hinge structure shows that His229 is capable of forming hydrogen bonds with surrounding residues. These observations led us to hypothesize that the imidazole ring of His229 may function to facilitate the cleavage by forming a transient radical center that is capable of extracting a proton from neighboring residues. The work presented here suggests the feasibility of engineering a new generation of monoclonal antibodies capable of resisting hinge cleavage to improve product stability and efficacy. 相似文献
110.
Topors is a DNA topoisomerase I- and p53-binding protein, and mainly functions as a p53 regulator. Accumulating evidence also
supports the notion that Topors plays the role as a negative regulator of cell growth, and possibly as a tumor suppressor.
Here, we demonstrated that Topors is also involved in normal mitotic progression, since Topors depletion delays mitotic entry
and affects mitotic progression. Furthermore, Topors is degradated in response to the activation of the spindle checkpoint.
Significantly, Polo-like kinase 1 (Plk1)-associated phosphorylation of Topors at S718 is essential for nocodazole-induced
degradation of Topors. 相似文献