全文获取类型
收费全文 | 1752篇 |
免费 | 220篇 |
国内免费 | 19篇 |
出版年
2022年 | 13篇 |
2021年 | 26篇 |
2020年 | 14篇 |
2019年 | 15篇 |
2018年 | 21篇 |
2017年 | 17篇 |
2016年 | 38篇 |
2015年 | 96篇 |
2014年 | 86篇 |
2013年 | 94篇 |
2012年 | 126篇 |
2011年 | 112篇 |
2010年 | 95篇 |
2009年 | 69篇 |
2008年 | 91篇 |
2007年 | 73篇 |
2006年 | 84篇 |
2005年 | 76篇 |
2004年 | 64篇 |
2003年 | 71篇 |
2002年 | 58篇 |
2001年 | 65篇 |
2000年 | 59篇 |
1999年 | 56篇 |
1998年 | 26篇 |
1997年 | 35篇 |
1996年 | 18篇 |
1995年 | 20篇 |
1994年 | 26篇 |
1993年 | 15篇 |
1992年 | 37篇 |
1991年 | 31篇 |
1990年 | 32篇 |
1989年 | 20篇 |
1988年 | 21篇 |
1987年 | 26篇 |
1986年 | 10篇 |
1985年 | 21篇 |
1984年 | 8篇 |
1983年 | 12篇 |
1982年 | 10篇 |
1980年 | 10篇 |
1979年 | 10篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1975年 | 6篇 |
1974年 | 6篇 |
1973年 | 5篇 |
1972年 | 8篇 |
1968年 | 6篇 |
排序方式: 共有1991条查询结果,搜索用时 31 毫秒
971.
Objective
To evaluate the functional and oncological outcomes of anterolateral thigh flap reconstruction for salvage laryngopharyngectomy after concurrent chemoradiotherapy for patients with hypopharyngeal carcinoma.Materials/Methods
A retrospective review was conducted on patients who underwent pharyngoesophageal reconstruction using anterolateral thigh flap after salvage laryngopharyngectomy for recurrent hypopharyngeal carcinoma between June 2003 and May 2010 at Chang Gung Memorial Hospital. The perioperative morbidity, mortality, functional outcomes, and oncological outcomes were evaluated.Results
33 patients were entered into the study. The mean follow-up time was 19.5±12.3 months. Recurrent pathological TNM stages included 3 (9.1%), 2 (6.1%), and 28 (84.8%) patients with stage II, III, and IV disease, respectively. Mean ICU stay was 10.3 days and the mean hospital stay was 39.9 days. Peri-operative mortality occurred in one patient (3%). 16 patients (48.5%) developed recipient site complications. Among them, 14 patients (42.4%) developed fistulas and 9 patients (27.3%) developed strictures. Except for 4 patients (12.1%), all achieved varying degree of oral intake with 29 patients (60.6%) being completely independent from tube feeding. The mean interval to start oral intake was 15.1 days. The 5-year overall survival and disease–free survival rates were 51.8% and 53.7%, respectively. The pN status is an independent predictor of overall survival and disease–free survival (P = 0.027 and 0.038, respectively).Conclusion
Pharyngoesophageal reconstruction after salvage laryngopharyngectomy remains challenging even in the experienced hands. Reconstructive microsurgeons who are prepared to take on these cases should be equally well prepared to manage the potential postoperative complications. 相似文献972.
Osamu Yamanaka Yong Yuan Vivien Jane Coulson-Thomas Tarsis Ferreira Gesteira Mindy K. Call Yujin Zhang Jianhua Zhang Shao-Hsuan Chang Changchun Xie Chia-Yang Liu Shizuya Saika James V. Jester Winston W-Y Kao 《PloS one》2013,8(12)
Lumican (Lum), a small leucine-rich proteoglycan (SLRP) family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing. Transforming growth factor-β receptor 1 (ALK5) was identified as a potential Lum-interacting protein through in silico molecular docking and molecular dynamics. This finding was verified by biochemical pull-down assays. Moreover, the Lum function on wound healing was abrogated by an ALK5-specific chemical inhibitor as well as by ALK5 shRNAi. Finally, we demonstrated that eukaryote-specific post-translational modifications are not required for the wound healing activity of Lum, as recombinant GST-Lum fusion proteins purified from E. coli and a chemically synthesized LumC13 peptide (the last C-terminal 13 amino acids of Lum) have similar effects on wound healing in vitro and in vivo. 相似文献
973.
974.
Quansheng Zhu Weixin Liu Liyo Kao Rustam Azimov Debra Newman Natalia Abuladze Ira Kurtz 《The Journal of biological chemistry》2013,288(11):7894-7906
In the kidney proximal tubule, NBCe1-A plays a critical role in absorbing HCO3− from cell to blood. NBCe1-A transmembrane segment 1 (TM1) is involved in forming part of the ion permeation pathway, and a missense mutation S427L in TM1 impairs ion transport, causing proximal renal tubular acidosis. In the present study, we examined the topology of NBCe1-A-TM1 in detail and its structural perturbation induced by S427L. We analyzed the N-terminal cytoplasmic region (Cys-389–Gln-424) of NBCe1-A-TM1 using the substituted cysteine scanning accessibility method combined with extensive chemical stripping, in situ chemical probing, and functional transport assays. NBCe1-A-TM1 was previously modeled on the anion exchanger 1 TM1 (AE1-TM1); however, our data demonstrated that the topology of AE1-TM1 differs significantly from NBCe1-A-TM1. Our findings revealed that NBCe1-A-TM1 is unusually long, consisting of 31 membrane-embedded amino acids (Phe-412 to Thr-442). The linker region (Arg-394–Pro-411) between the N terminus of TM1 and the cytoplasmic domain is minimally exposed to aqueous and is potentially folded in a helical structure that intimately interacts with the NBCe1-A cytoplasmic domain. In contrast, AE1-TM1 contains 25 amino acids connected to an aqueous-exposed cytoplasmic region. Based on our new NBCe1-A-TM1 model, Ser-427 resides in the middle of TM1. Leucine substitution at Ser-427 blocks the normal aqueous access to Thr-442, Ala-435, and Lys-404, implying a significant alteration of NBCe1-TM1 orientation. Our study provides novel structural insights into the pathogenic mechanism of S427L in mediating proximal renal tubular acidosis. 相似文献
975.
Bing-Wen Soong Yen-Hua Huang Pei-Chien Tsai Chien-Chang Huang Hung-Chuan Pan Yi-Chun Lu Hsin-Ju Chien Tze-Tze Liu Ming-Hong Chang Kon-Ping Lin Pang-Hsien Tu Lung-Sen Kao Yi-Chung Lee 《American journal of human genetics》2013,92(3):422-430
Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited neuropathies. Mutations in approximately 45 genes have been identified as being associated with CMT. Nevertheless, the genetic etiologies of at least 30% of CMTs have yet to be elucidated. Using a genome-wide linkage study, we previously mapped a dominant intermediate CMT to chromosomal region 3q28–q29. Subsequent exome sequencing of two affected first cousins revealed heterozygous mutation c.158G>A (p.Gly53Asp) in GNB4, encoding guanine-nucleotide-binding protein subunit beta-4 (Gβ4), to cosegregate with the CMT phenotype in the family. Further analysis of GNB4 in an additional 88 unrelated CMT individuals uncovered another de novo mutation, c.265A>G (p.Lys89Glu), in this gene in one individual. Immunohistochemistry studies revealed that Gβ4 was abundant in the axons and Schwann cells of peripheral nerves and that expression of Gβ4 was significantly reduced in the sural nerve of the two individuals carrying the c.158G>A (p.Gly53Asp) mutation. In vitro studies demonstrated that both the p.Gly53Asp and p.Lys89Glu altered proteins impaired bradykinin-induced G-protein-coupled-receptor (GPCR) signaling, which was facilitated by the wild-type Gβ4. This study identifies GNB4 mutations as a cause of CMT and highlights the importance of Gβ4-related GPCR signaling in peripheral-nerve function in humans. 相似文献
976.
Previous literature on racial self-identification among multiracials demonstrates that self-identification differs by context. Moreover, among multiracial adolescents, identity, usually measured in school, is correlated with achievement. In addition, a few studies have indicated that for half-white, half-minority adolescents, school achievement falls in between the achievements of their monoracial counterparts. Using the in-school and in-home components of the National Longitudinal Study of Adolescent Health (Add Health), we examine the relationship between racial self-identification and school belonging and achievement. We find that among black/white and Asian/white adolescents, adolescents who self-identify as white are particularly disadvantaged in school, reporting lower grade point averages (GPA) than their multiracial counterparts. Our conclusions suggest that multiple contextual measures of self-identification better capture the relationship between racial identification and academic achievement among multiracial adolescents. 相似文献
977.
Lateral roots (LRs) perform the essential tasks of providing water, nutrients, and physical support to plants. Therefore, understanding the regulation of LR development is of agronomic importance. Recent findings suggest that heme oxygenase (HO) plays an important role in LR development. In this study, we examined the effect of cobalt chloride (CoCl2) on LR formation and HO expression in rice. Treatment with CoCl2 induced LR formation and HO activity. We further observed that CoCl2 could induce the expression of OsHO1 but not OsHO2. CoCl2-increased HO activity occurred before LR formation. Zinc protoporphyrin IX (ZnPPIX, the specific inhibitor of HO) and hemoglobin (the carbon monoxide/nitric oxide scavenger) reduced LR formation, HO activity, and OsHO1 expression. Application of biliverdin, a product of HO-catalyzed reaction, to CoCl2-treated rice seedlings reversed the ZnPPIX-inhibited LR formation and ZnPPIX-decreased HO activity. CoCl2 had no effect on H2O2 content and nitric oxide production. Moreover, application of ascorbate, a H2O2 scavenger, failed to affect CoCl2-promoted LR formation and HO activity. It is concluded that HO is required for CoCl2-promoted LR formation in rice. 相似文献
978.
Adrienne Tin Brad C. Astor Eric Boerwinkle Ron C. Hoogeveen Josef Coresh Wen Hong Linda Kao 《Human genetics》2013,132(6):619-627
Beta-2 microglobulin (B2M) is a component of the major histocompatibility complex (MHC) class I molecule and has been studied as a biomarker of kidney function, cardiovascular diseases and mortality. Little is known about the genes influencing its levels directly or through glomerular filtration rate (GFR). We conducted a genome-wide association study of plasma B2M levels in 6738 European Americans from the Atherosclerosis Risk in Communities study to identify novel loci for B2M and assessed its association with known estimated GFR (eGFR) loci. We identified 2 genome-wide significant loci. One was in the human leukocyte antigen (HLA) region on chromosome 6 (lowest p value = 1.8 × 10?23 for rs9264638). At this locus, 6 index SNPs accounted for 3.2 % of log(B2M) variance, and their association with B2M could largely be explained by imputed classical alleles of the MHC class I genes: HLA-A, HLA-B, or HLA-C. The index SNPs at this locus were not associated with eGFR based on serum creatinine (eGFRcr). The other locus of B2M was on chromosome 12 (rs3184504 at SH2B3, beta = 0.02, p value = 3.1 × 10?8), which was previously implicated as an eGFR locus. In conclusion, although B2M is known to be a component of MHC class I molecule, the association between HLA class I alleles and plasma B2M levels in a community-based population is novel. The identification of the two novel loci for B2M extends our understanding of its metabolism and informs its use as a kidney filtration biomarker. 相似文献
979.
980.
Jim Waterhouse Shaoyuan Kao Benjamin Edwards Greg Atkinson Thomas Reilly 《Chronobiology international》2013,30(5):985-1007
To understand better how disruption to daily routines and circadian factors affect food intake, some aspects of 361 passengers' eating habits during long‐haul flights across eight time zones were investigated. Two meals were provided during each flight. Passengers stated whether or not they had eaten part or all of each meal and the reasons for this decision. They were also asked to give their responses to it (appetite beforehand, enjoyment during the meal, and satiety afterwards), and the type of meal they would prefer to have eaten, given an unrestricted choice. There were few occasions (<6%) when a meal was refused altogether, and no single reason was dominant. Subjective responses to food intake were more positive when larger meals were eaten and “appetite” rather than “no choice” was given as the reason for eating. Subjective responses were also more positive in those who thought the size of the meal offered was neither too small nor too large. When the two meals were considered separately, the first meal was well received by the passengers, and their enjoyment of it was not significantly different from “normal.” The second meal (offered soon before landing in the new time zone) was less well received, and many passengers would have preferred a smaller meal. The findings contribute to an understanding of the factors determining the decision to eat a meal and the subjective responses to the food that is eaten. They also have implications for airlines wishing to provide food that is acceptable to passengers and for those providing meals for night workers. 相似文献