全文获取类型
收费全文 | 7573篇 |
免费 | 546篇 |
国内免费 | 694篇 |
出版年
2024年 | 15篇 |
2023年 | 86篇 |
2022年 | 233篇 |
2021年 | 406篇 |
2020年 | 299篇 |
2019年 | 347篇 |
2018年 | 323篇 |
2017年 | 265篇 |
2016年 | 358篇 |
2015年 | 498篇 |
2014年 | 562篇 |
2013年 | 612篇 |
2012年 | 762篇 |
2011年 | 642篇 |
2010年 | 362篇 |
2009年 | 365篇 |
2008年 | 387篇 |
2007年 | 328篇 |
2006年 | 288篇 |
2005年 | 238篇 |
2004年 | 206篇 |
2003年 | 175篇 |
2002年 | 152篇 |
2001年 | 151篇 |
2000年 | 115篇 |
1999年 | 100篇 |
1998年 | 68篇 |
1997年 | 71篇 |
1996年 | 70篇 |
1995年 | 54篇 |
1994年 | 49篇 |
1993年 | 31篇 |
1992年 | 41篇 |
1991年 | 20篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 11篇 |
1985年 | 18篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1966年 | 1篇 |
1965年 | 2篇 |
排序方式: 共有8813条查询结果,搜索用时 15 毫秒
971.
目的:观察小梁切除术中应用丝裂霉素C(MMC)对角膜内皮细胞的影响。方法:收集2010年9月2011年5月在我院行小梁切除术的青光眼患者60例(78眼),随机分为术中应用丝裂霉素C的36例(46眼)患者为A组,术中不用丝裂霉素C的24例(32眼)为B组,分别观察术前、术后1个月和术后3个月两组眼压(IOP)、角膜内皮细胞的密度(CD)、平均细胞面积(AVG)及细胞面积变异系数(CV),分析其数量的改变及两组间的差异。结果:A组术前眼压为(35.4±13.7)mmHg,B组术前眼压为(32.5±13.5)mmHg差异无统计学意义(P>0.05),A组术后1个月及术后3个月眼压分别为(15.7±3.7)mmHg、(17.0±3.2)mmHg,均低于B组的(19.4±3.7)mmHg、(20.2±2.1)mmHg,差异有统计学意义(P<0.05)。A组术前、术后1个月及术后3个月角膜内皮细胞密度分别为(2475±484)个/mm2、(2199±373)个/mm2、(2164±332)个/mm2;平均细胞面积分别为(431.4±67.6)μm2、(480.6±66.8)μm2、(463.8±46.2)μm2;细胞面积变异系数分别为(31.1±7.4)%、(34.4±6.3)%、(31.2±7.5)%;术后1个月及术后3个月各参数与术前比较,差异均有统计学意义(P<0.05)。B组术前、术后1个月及术后3个月角膜内皮细胞密度分别为(2342±94)个/mm2、(2185±215)个/mm2、(2074±218)个/mm2;平均细胞面积分别为(453.9±94.8)μm2、(516.3±100.8)μm2、(499.81±106.4)μm2;细胞面积变异系数分别为(30.2±3.0)%、(32.7±2.9)%、(31.4±4.3)%;除术后3个月角膜内皮细胞与术前比较有意义(P<0.05)外,余参数术后1个月及术后3个月与术前比较差异均无统计学意义(P>0.05)。术后1个月A组的角膜内皮细胞丢失率为10.4%高于B组的6.1%,差异有统计学意义(P<0.05);术后3个月A组的角膜内皮细胞丢失率为11.1%高于B组的10.0%,差异无统计学意义(P>0.05)。结论:小梁切除术中用丝裂霉素C的降压效果比不用丝裂霉素C的效果好,但短期内前者角膜内皮细胞的丢失率高于后者。 相似文献
972.
Tao Zhou Huaijie Jia Guohua Chen Xiaobing He Yongxiang Fang Xiaoxia Wang Qisai Guan Shuang Zeng Qing Cui Zhizhong Jing 《Virology journal》2012,9(1):25
Background
Sheeppox virus (SPPV) and goatpox virus (GTPV), members of the Capripoxvirus genus of the Poxviridae family are causative agents of sheep pox and goat pox respectively, which are important contagious diseases and endemic in central and northern Africa, the Middle and Far East, and the Indian sub-continent. Both sheep pox and goat pox can cause wool and hide damage, and reduce the production of mutton and milk, which may result in significant economic losses and threaten the stockbreeding. In this study, three SPPVs and two GTPVs were collected from China in 2009 and 2011. We described the sequence features and phylogenetic analysis of the P32 gene, GPCR gene and RPO30 gene of the SPPVs and GTPVs to reveal their genetic relatedness.Results
Sequence and phylogenetic analysis showed that there was a close relationship among SPPV/GanS/2/2011/China, SPPV/GanS/1/2011/China and SPPV/NingX/2009/China. They were clustered on the same SPPV clade. GTPV/HuB/2009/China and GS-V1 belonged to the GTPV lineage. GS-V1 was closely related to other GTPV vaccine strains. GTPV/HuB/2009/China and GS-V1 were clustered with GTPVs from China and some southern Asian countries.Conclusion
This study may expand the datum for spread trend research of Chinese SPPVs and GTPVs, meanwhile provide theoretical references to improve the preventive and control strategy.973.
Cui J Chen S Zhang C Meng F Wu W Hu R Hadass O Lehmidi T Blair GJ Lee M Chang M Mobashery S Sun GY Gu Z 《Molecular neurodegeneration》2012,7(1):21-15
ABSTRACT: BACKGROUND: Cerebral ischemia has been shown to induce activation of matrix metalloproteinases (MMPs), particularly MMP-9, which is associated with impairment of the neurovasculature, resulting in blood-brain barrier breakdown, hemorrhage and neurodegeneration. We previously reported that the thiirane inhibitor SB-3CT, which is selective for gelatinases (MMP-2 and 9), could antagonize neuronal apoptosis after transient focal cerebral ischemia. RESULTS: Here, we used a fibrin-rich clot to occlude the middle cerebral artery (MCA) and assessed the effects of SB-3CT on the neurovasculature. Results show that neurobehavioral deficits and infarct volumes induced by embolic ischemia are comparable to those induced by the filament-occluded transient MCA model. Confocal microscopy indicated embolus-blocked brain microvasculature and neuronal cell death. Post-ischemic SB-3CT treatment attenuated infarct volume, ameliorated neurobehavioral outcomes, and antagonized the increases in levels of proform and activated MMP-9. Embolic ischemia caused degradation of the neurovascular matrix component laminin and tight-junction protein ZO-1, contraction of pericytes, and loss of lectin-positive brain microvessels. Despite the presence of the embolus, SB-3CT mitigated these outcomes and reduced hemorrhagic volumes. Interestingly, SB-3CT treatment for seven days protected against neuronal laminin degradation and protected neurons from ischemic cell death. CONCLUSION: These results demonstrate considerable promise for the thiirane class of selective gelatinase inhibitors as potential therapeutic agents in stroke therapy. 相似文献
974.
Jun Liu Qiao-Chu Wang Fei Wang Xing Duan Xiao-Xin Dai Teng Wang Hong-Lin Liu Xiang-Shun Cui Nam-Hyung Kim Shao-Chen Sun 《PloS one》2012,7(12)
The actin nucleation factor Arp2/3 complex is a main regulator of actin assembly and is involved in multiple processes like cell migration and adhesion, endocytosis, and the establishment of cell polarity in mitosis. Our previous work showed that the Arp2/3 complex was involved in the actin-mediated mammalian oocyte asymmetric division. However, the regulatory mechanisms and signaling pathway of Arp2/3 complex in meiosis is still unclear. In the present work, we identified that the nucleation promoting factors (NPFs) JMY and WAVE2 were necessary for the expression and localization of Arp2/3 complex in mouse oocytes. RNAi of both caused the degradation of actin cap intensity, indicating the roles of NPFs in the formation of actin cap. Moreover, JMY and WAVE2 RNAi decreased the expression of ARP2, a key component of Arp2/3 complex. However, knock down of Arp2/3 complex by Arpc2 and Arpc3 siRNA microinjection did not affect the expression and localization of JMY and WAVE2. Our results indicate that the NPFs, JMY and WAVE2, are upstream regulators of Arp2/3 complex in mammalian oocyte asymmetric division. 相似文献
975.
976.
Rahman AH Cui W Larosa DF Taylor DK Zhang J Goldstein DR Wherry EJ Kaech SM Turka LA 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(6):3804-3810
During acute lymphocytic choriomeningitis virus (LCMV) infection, CD8 T cells rapidly expand and differentiate into effectors that are required for viral clearance. The accumulation of activated T cells is greatly reduced in mice lacking the adaptor molecule MyD88. Although MyD88 has generally been considered to indirectly regulate adaptive immune responses by controlling inflammatory cytokine production and Ag presentation in innate immune cells, in this study, we identify an unappreciated cell-intrinsic role for MyD88 in LCMV-specific CD8 T cells. Using reciprocal adoptive transfer models and bone marrow chimeras, we show that Myd88(-/-) CD8 T cells are defective in their clonal expansion in response to LCMV infection, independent of their environment. Furthermore, we show that while MyD88 is dispensable for initial activation and division of LCMV-specific CD8 T cells during the early stages of viral infection, MyD88-dependent signals are critical for supporting their survival and sustained accumulation. 相似文献
977.
Arginine 352 (R352) in the sixth transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) previously
was reported to form an anion/cation selectivity filter and to provide positive charge in the intracellular vestibule. However,
mutations at this site have nonspecific effects, such as inducing susceptibility of endogenous cysteines to chemical modification.
We hypothesized that R352 stabilizes channel structure and that charge-destroying mutations at this site disrupt pore architecture,
with multiple consequences. We tested the effects of mutations at R352 on conductance, anion selectivity and block by the
sulfonylurea drug glipizide, using recordings of wild-type and mutant channels. Charge-altering mutations at R352 destabilized
the open state and altered both selectivity and block. In contrast, R352K-CFTR was similar to wild-type. Full conductance
state amplitude was similar to that of wild-type CFTR in all mutants except R352E, suggesting that R352 does not itself form
an anion coordination site. In an attempt to identify an acidic residue that may interact with R352, we found that permeation
properties were similarly affected by charge-reversing mutations at D993. Wild-type-like properties were rescued in R352E/D993R-CFTR,
suggesting that R352 and D993 in the wild-type channel may interact to stabilize pore architecture. Finally, R352A-CFTR was
sensitive to modification by externally applied MTSEA+, while wild-type and R352E/D993R-CFTR were not. These data suggest that R352 plays an important structural role in CFTR,
perhaps reflecting its involvement in forming a salt bridge with residue D993. 相似文献
978.
Conventional myosin is representative of biomolecular motors in which the hydrolysis of adenosine triphosphate (ATP) is coupled to large-scale structural transitions both in and remote from the active site. The mechanism that underlies such “mechanochemical coupling,” especially the causal relationship between hydrolysis and allosteric structural changes, has remained elusive despite extensive experimental and computational analyses. In this study, using combined quantum mechanical and molecular mechanical simulations and different conformations of the myosin motor domain, we provide evidence to support that regulation of ATP hydrolysis activity is not limited to residues in the immediate environment of the phosphate. Specifically, we illustrate that efficient hydrolysis of ATP depends not only on the proper orientation of the lytic water but also on the structural stability of several nearby residues, especially the Arg238-Glu459 salt bridge (the numbering of residues follows myosin II in Dictyostelium discoideum) and the water molecule that spans this salt bridge and the lytic water. More importantly, by comparing the hydrolysis activities in two motor conformations with very similar active-site (i.e., Switches I and II) configurations, which distinguished this work from our previous study, the results clearly indicate that the ability of these residues to perform crucial electrostatic stabilization relies on the configuration of residues in the nearby N-terminus of the relay helix and the “wedge loop.” Without the structural support from those motifs, residues in a closed active site in the post-rigor motor domain undergo subtle structural variations that lead to consistently higher calculated ATP hydrolysis barriers than in the pre-powerstroke state. In other words, starting from the post-rigor state, turning on the ATPase activity requires not only displacement of Switch II to close the active site but also structural transitions in the N-terminus of the relay helix and the “wedge loop,” which have been proposed previously to be ultimately coupled to the rotation of the converter subdomain 40 Å away. 相似文献
979.
The genetic basis of complex diseases is expected to be highly heterogeneous, with complex interactions among multiple disease loci and environment factors. Due to the multi-dimensional property of interactions among large number of genetic loci, efficient statistical approach has not been well developed to handle the high-order epistatic complexity. In this article, we introduce a new approach for testing genetic epistasis in multiple loci using an entropy-based statistic for a case-only design. The entropy-based statistic asymptotically follows a χ2 distribution. Computer simulations show that the entropy-based approach has better control of type I error and higher power compared to the standard χ2 test. Motivated by a schizophrenia data set, we propose a method for measuring and testing the relative entropy of a clinical phenotype, through which one can test the contribution or interaction of multiple disease loci to a clinical phenotype. A sequential forward selection procedure is proposed to construct a genetic interaction network which is illustrated through a tree-based diagram. The network information clearly shows the relative importance of a set of genetic loci on a clinical phenotype. To show the utility of the new entropy-based approach, it is applied to analyze two real data sets, a schizophrenia data set and a published malaria data set. Our approach provides a fast and testable framework for genetic epistasis study in a case-only design. 相似文献
980.
Data on social organization of two bands of black-and-white snub-nosed monkeys (Rhinopithecus bieti) were collected when the monkeys were crossing an open spot at Nanren and Bamei (northwest of Yunnan, China) using a sampling rule where individuals within one social unit are spatially closer to each other than individuals between social units. The typical pattern of social organization in this sample was multiple adult females (AFs) and their offspring with one adult male (AM) in a one-male unit (OMU), similar to that of many other colobines. In such units, on average one male is associated with 4.0 AFs and 2.5 of their offspring. Moreover, there are multimale/multifemale units and monogamous units besides OMUs. All bisexual units traveled together with at least one all-male unit as a cohesive band. In two bands of monkeys, 87% of AMs in bisexual units were within OMUs, 7.8% within monogamous units and 5.2% within multimale, multifemale units. In the Bamei band, 6.7% of AMs were in the all-male unit. The size of OMUs in the Nanren band was larger than that of the Bamei band, with more AFs and juveniles, which may be related to better conservation in the Nanren band's habitat. For the Nanren band, the average number of AFs in OMUs varied across time, increasing from 4.3 in 1994 to 5.1 in 2001, and then decreasing to 3.8 in 2005. This article suggests three possible explanations for this variation, but more data are needed for these hypotheses to be tested. 相似文献