全文获取类型
收费全文 | 9077篇 |
免费 | 759篇 |
国内免费 | 9篇 |
出版年
2023年 | 48篇 |
2022年 | 51篇 |
2021年 | 154篇 |
2020年 | 130篇 |
2019年 | 113篇 |
2018年 | 227篇 |
2017年 | 183篇 |
2016年 | 300篇 |
2015年 | 398篇 |
2014年 | 433篇 |
2013年 | 555篇 |
2012年 | 698篇 |
2011年 | 672篇 |
2010年 | 437篇 |
2009年 | 384篇 |
2008年 | 564篇 |
2007年 | 566篇 |
2006年 | 476篇 |
2005年 | 449篇 |
2004年 | 449篇 |
2003年 | 437篇 |
2002年 | 365篇 |
2001年 | 122篇 |
2000年 | 100篇 |
1999年 | 89篇 |
1998年 | 99篇 |
1997年 | 56篇 |
1996年 | 50篇 |
1995年 | 61篇 |
1994年 | 56篇 |
1993年 | 38篇 |
1992年 | 60篇 |
1991年 | 52篇 |
1990年 | 62篇 |
1989年 | 58篇 |
1988年 | 52篇 |
1987年 | 49篇 |
1986年 | 47篇 |
1985年 | 41篇 |
1984年 | 65篇 |
1983年 | 38篇 |
1982年 | 48篇 |
1981年 | 54篇 |
1980年 | 55篇 |
1979年 | 34篇 |
1978年 | 39篇 |
1977年 | 30篇 |
1976年 | 32篇 |
1974年 | 33篇 |
1973年 | 25篇 |
排序方式: 共有9845条查询结果,搜索用时 15 毫秒
1.
Aruna S. Jaiswal Harekrushna Panda Brian K. Law Jay Sharma Jitesh Jani Robert Hromas Satya Narayan 《PloS one》2015,10(5)
Recently approved chemotherapeutic agents to treat colorectal cancer (CRC) have made some impact; however, there is an urgent need for newer targeted agents and strategies to circumvent CRC growth and metastasis. CRC frequently exhibits natural resistance to chemotherapy and those who do respond initially later acquire drug resistance. A mechanism to potentially sensitize CRC cells is by blocking the DNA polymerase β (Pol-β) activity. Temozolomide (TMZ), an alkylating agent, and other DNA-interacting agents exert DNA damage primarily repaired by a Pol-β-directed base excision repair (BER) pathway. In previous studies, we used structure-based molecular docking of Pol-β and identified a potent small molecule inhibitor (NSC666715). In the present study, we have determined the mechanism by which NSC666715 and its analogs block Fen1-induced strand-displacement activity of Pol-β-directed LP-BER, cause apurinic/apyrimidinic (AP) site accumulation and induce S-phase cell cycle arrest. Induction of S-phase cell cycle arrest leads to senescence and apoptosis of CRC cells through the p53/p21 pathway. Our initial findings also show a 10-fold reduction of the IC50 of TMZ when combined with NSC666715. These results provide a guide for the development of a target-defined strategy for CRC chemotherapy that will be based on the mechanisms of action of NSC666715 and TMZ. This combination strategy can be used as a framework to further reduce the TMZ dosages and resistance in CRC patients. 相似文献
2.
3.
Phylogeography and population differentiation in the Psittacanthus calyculatus (Loranthaceae) mistletoe: a complex scenario of climate–volcanism interaction along the Trans‐Mexican Volcanic Belt 下载免费PDF全文
4.
Roberto López-Píriz Eva Solá-Linares Mercedes Rodriguez-Portugal Beatriz Malpica Idoia Díaz-Güemes Silvia Enciso Leticia Esteban-Tejeda Belén Cabal Juan José Granizo José Serafín Moya Ramón Torrecillas 《PloS one》2015,10(10)
ObjectivesThe aim of the present study is to evaluate, in a ligature-induced peri-implantitis model, the efficacy of three antimicrobial glassy coatings in the prevention of biofilm formation, intrasulcular bacterial growth and the resulting peri-implant bone loss.MethodsMandibular premolars were bilaterally extracted from five beagle dogs. Four dental implants were inserted on each hemiarch. Eight weeks after, one control zirconia abutment and three with different bactericidal coatings (G1n-Ag, ZnO35, G3) were connected. After a plaque control period, bacterial accumulation was allowed and biofilm formation on abutments was observed by Scanning Electron Microscopy (SEM). Peri-implantitis was induced by cotton ligatures. Microbial samples and peri-implant crestal bone levels of all implant sites were obtained before, during and after the breakdown period.ResultsDuring experimental induce peri-implantitis: colony forming units counts from intrasulcular microbial samples at implants with G1n-Ag coated abutment remained close to the basal inoculum; G3 and ZnO35 coatings showed similar low counts; and anaerobic bacterias counts at control abutments exhibited a logarithmic increase by more than 2. Bone loss during passive breakdown period was no statistically significant. Additional bone loss occurred during ligature-induce breakdown: 0.71 (SD 0.48) at G3 coating, 0.57 (SD 0.36) at ZnO35 coating, 0.74 (SD 0.47) at G1n-Ag coating, and 1.29 (SD 0.45) at control abutments; and statistically significant differences (p<0.001) were found. The lowest bone loss at the end of the experiment was exhibited by implants dressing G3 coated abutments (mean 2.1; SD 0.42).SignificanceAntimicrobial glassy coatings could be a useful tool to ward off, diminish or delay peri-implantitis progression. 相似文献
5.
6.
A perturbation framework is developed to analyze metastable behavior in stochastic processes with random internal and external states. The process is assumed to be under weak noise conditions, and the case where the deterministic limit is bistable is considered. A general analytical approximation is derived for the stationary probability density and the mean switching time between metastable states, which includes the pre exponential factor. The results are illustrated with a model of gene expression that displays bistable switching. In this model, the external state represents the number of protein molecules produced by a hypothetical gene. Once produced, a protein is eventually degraded. The internal state represents the activated or unactivated state of the gene; in the activated state the gene produces protein more rapidly than the unactivated state. The gene is activated by a dimer of the protein it produces so that the activation rate depends on the current protein level. This is a well studied model, and several model reductions and diffusion approximation methods are available to analyze its behavior. However, it is unclear if these methods accurately approximate long-time metastable behavior (i.e., mean switching time between metastable states of the bistable system). Diffusion approximations are generally known to fail in this regard. 相似文献
7.
8.
9.
Bo Ram Kim Ji-Young Park Hyung Jae Jeong Hyung-Jun Kwon Su-Jin Park In-Chul Lee 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1256-1265
Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound 5e was the most potent inhibitor of S. pneumoniae sialidase (IC50?=?0.2?±?0.1?µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity 5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections. 相似文献
10.