全文获取类型
| 收费全文 | 2198篇 |
| 免费 | 109篇 |
| 国内免费 | 40篇 |
专业分类
| 2347篇 |
出版年
| 2024年 | 27篇 |
| 2023年 | 19篇 |
| 2022年 | 64篇 |
| 2021年 | 111篇 |
| 2020年 | 75篇 |
| 2019年 | 94篇 |
| 2018年 | 69篇 |
| 2017年 | 60篇 |
| 2016年 | 88篇 |
| 2015年 | 158篇 |
| 2014年 | 153篇 |
| 2013年 | 173篇 |
| 2012年 | 213篇 |
| 2011年 | 182篇 |
| 2010年 | 104篇 |
| 2009年 | 93篇 |
| 2008年 | 131篇 |
| 2007年 | 83篇 |
| 2006年 | 96篇 |
| 2005年 | 77篇 |
| 2004年 | 77篇 |
| 2003年 | 48篇 |
| 2002年 | 52篇 |
| 2001年 | 7篇 |
| 2000年 | 6篇 |
| 1999年 | 19篇 |
| 1998年 | 15篇 |
| 1997年 | 6篇 |
| 1996年 | 5篇 |
| 1995年 | 9篇 |
| 1994年 | 4篇 |
| 1993年 | 4篇 |
| 1992年 | 1篇 |
| 1991年 | 2篇 |
| 1989年 | 3篇 |
| 1987年 | 2篇 |
| 1984年 | 2篇 |
| 1983年 | 2篇 |
| 1982年 | 4篇 |
| 1981年 | 1篇 |
| 1980年 | 3篇 |
| 1979年 | 1篇 |
| 1977年 | 2篇 |
| 1974年 | 1篇 |
| 1973年 | 1篇 |
排序方式： 共有2347条查询结果，搜索用时 31 毫秒
951.
Lina Cai Xiaojiao Zhao Tao Jiang Juanjuan Qiu Lawrence Owusu Yufang Ma Bo Wang Yi Xin 《Indian journal of microbiology》2014,54(1):46-51
Decaprenylphosphoryl-d-arabinofuranosyl (DPA), the immediate donor for the polymerized d-Araf residues of mycobacterial arabinan, is synthesized from 5-phosphoribose-1-diphosphate (PRPP) in three-step reactions. (i) PRPP is transferred to decaprenyl-phosphate (DP) to form decaprenylphosphoryl-d-5-phosphoribose (DPPR). (ii) DPPR is dephosphorylated to form decaprenylphosphoryl-d-ribose (DPR). (iii) DPR is formed to DPA by the epimerase. Mycobacterium tuberculosis Rv3806c and heteromeric Rv3790/Rv3791 have been identified as the PRPP: decaprenyl-phosphate 5-phosphoribosyltransferase and the epimerase respectively. Rv3807c, however, as the candidate of phospholipid phosphatase, catalyzing the biosynthesis of decapreny-l-phosphoryl-ribose (DPR) from decaprenylphosphoryl-β-d-5-phosphoribose by dephosphorylating, has no direct experimental evidence of its essentiality in any species of mycobacterium. In this study, Rv3807c gene was amplified from the genome of M. tuberculosis H37Rv by PCR, and was successfully expressed in Escherichia coli BL21 (DE3) via the recombinant plasmid pColdII-Rv3807c. The resulting protein with the 6× His-tag was identified by SDS-PAGE and Western blotting. The protein was predicted through bioinformatics to contain three transmembrane domains, the N-terminal peptide, and a core structure with phosphatidic acid phosphatase type2/haloperoxidase. This study provides biochemical and bioinformatics evidence for the importance of Rv3807c in mycobacteria, and further functional studies will be conducted for validating Rv3807c as a promising phospholipid phosphatase in the synthetic pathway of DPA. 相似文献
952.
953.
Purpose
To assess the efficacy of midazolam for anxiety control in third molar extraction surgery.Methods
Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team.Results
Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone.Conclusion
It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient’s respiratory function must be monitored closely, because multidrug sedation is also more risky. 相似文献954.
Giovanni Lo Iacono Andrew A. Cunningham Elisabeth Fichet-Calvet Robert F. Garry Donald S. Grant Sheik Humarr Khan Melissa Leach Lina M. Moses John S. Schieffelin Jeffrey G. Shaffer Colleen T. Webb James L. N. Wood 《PLoS neglected tropical diseases》2015,9(1)
Background
Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions.Methodology/Principal Findings
Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) , with a maximum value up to .Conclusions/Significance
This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection. 相似文献955.
Andrea Masotti Paolo Uva Laura Davis-Keppen Lina Basel-Vanagaite Lior Cohen Elisa Pisaneschi Antonella Celluzzi Paola Bencivenga Mingyan Fang Mingyu Tian Xun Xu Marco Cappa Bruno Dallapiccola 《American journal of human genetics》2015,96(2):295-300
Keppen-Lubinsky syndrome (KPLBS) is a rare disease mainly characterized by severe developmental delay and intellectual disability, microcephaly, large prominent eyes, a narrow nasal bridge, a tented upper lip, a high palate, an open mouth, tightly adherent skin, an aged appearance, and severe generalized lipodystrophy. We sequenced the exomes of three unrelated individuals affected by KPLBS and found de novo heterozygous mutations in KCNJ6 (GIRK2), which encodes an inwardly rectifying potassium channel and maps to the Down syndrome critical region between DIRK1A and DSCR4. In particular, two individuals shared an in-frame heterozygous deletion of three nucleotides (c.455_457del) leading to the loss of one amino acid (p.Thr152del). The third individual was heterozygous for a missense mutation (c.460G>A) which introduces an amino acid change from glycine to serine (p.Gly154Ser). In agreement with animal models, the present data suggest that these mutations severely impair the correct functioning of this potassium channel. Overall, these results establish KPLBS as a channelopathy and suggest that KCNJ6 (GIRK2) could also be a candidate gene for other lipodystrophies. We hope that these results will prompt investigations in this unexplored class of inwardly rectifying K+ channels. 相似文献
956.
María José Hernández-Corbacho Daniel Canals Mohamad M. Adada Mengling Liu Can E. Senkal Jae Kyo Yi Cungui Mao Chiara Luberto Yusuf A. Hannun Lina M. Obeid 《The Journal of biological chemistry》2015,290(42):25356-25373
Ceramide synthases (CerS1–CerS6), which catalyze the N-acylation of the (dihydro)sphingosine backbone to produce (dihydro)ceramide in both the de novo and the salvage or recycling pathway of ceramide generation, have been implicated in the control of programmed cell death. However, the regulation of the de novo pathway compared with the salvage pathway is not fully understood. In the current study, we have found that late accumulation of multiple ceramide and dihydroceramide species in MCF-7 cells treated with TNFα occurred by up-regulation of both pathways of ceramide synthesis. Nevertheless, fumonisin B1 but not myriocin was able to protect from TNFα-induced cell death, suggesting that ceramide synthase activity is crucial for the progression of cell death and that the pool of ceramide involved derives from the salvage pathway rather than de novo biosynthesis. Furthermore, compared with control cells, TNFα-treated cells exhibited reduced focal adhesion kinase and subsequent plasma membrane permeabilization, which was blocked exclusively by fumonisin B1. In addition, exogenously added C6-ceramide mimicked the effects of TNFα that lead to cell death, which were inhibited by fumonisin B1. Knockdown of individual ceramide synthases identified CerS6 and its product C16-ceramide as the ceramide synthase isoform essential for the regulation of cell death. In summary, our data suggest a novel role for CerS6/C16-ceramide as an upstream effector of the loss of focal adhesion protein and plasma membrane permeabilization, via the activation of caspase-7, and identify the salvage pathway as the critical mechanism of ceramide generation that controls cell death. 相似文献
957.
958.
为了研究一氧化氮(nitric oxide,NO)在气孔发育中的功能,本实验利用NO的释放剂硝普钠(SNP)处理拟南芥野生型,结果显示,SNP处理后的子叶气孔指数(SI)和%(GMC+M)都较未处理组明显升高。继续检测拟南芥内源一氧化氮升高的突变体nox1和内源一氧化氮降低的突变体noa1的气孔参数,结果显示,nox1的气孔指数(SI)和%(GMC+M)相对野生型明显提高,noa1的气孔指数(SI)和%(GMC+M)低于野生型。荧光定量PCR结果进一步显示,NO抑制了气孔发育相关基因MUTE,SCRM,SCRM2的表达。综上结果表明,NO通过调控气孔发育相关基因的表达影响气孔发育。 相似文献
959.
Hong Zheng Lina Zhang Yanrui Zhao Da Yang Fengju Song Yang Wen Quan Hao Zhibin Hu Wei Zhang Kexin Chen 《PloS one》2013,8(11)
Background
Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.Methodology/Principal Findings
We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validation sets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients.Conclusions/Significance
Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis. 相似文献960.