全文获取类型
收费全文 | 2004篇 |
免费 | 96篇 |
国内免费 | 25篇 |
专业分类
耳鼻咽喉 | 41篇 |
儿科学 | 65篇 |
妇产科学 | 13篇 |
基础医学 | 233篇 |
口腔科学 | 49篇 |
临床医学 | 231篇 |
内科学 | 317篇 |
皮肤病学 | 38篇 |
神经病学 | 111篇 |
特种医学 | 244篇 |
外科学 | 257篇 |
综合类 | 26篇 |
一般理论 | 2篇 |
预防医学 | 154篇 |
眼科学 | 56篇 |
药学 | 212篇 |
中国医学 | 4篇 |
肿瘤学 | 72篇 |
出版年
2021年 | 13篇 |
2020年 | 13篇 |
2019年 | 24篇 |
2018年 | 46篇 |
2017年 | 20篇 |
2016年 | 42篇 |
2015年 | 28篇 |
2014年 | 46篇 |
2013年 | 90篇 |
2012年 | 77篇 |
2011年 | 79篇 |
2010年 | 76篇 |
2009年 | 54篇 |
2008年 | 74篇 |
2007年 | 102篇 |
2006年 | 98篇 |
2005年 | 87篇 |
2004年 | 80篇 |
2003年 | 40篇 |
2002年 | 36篇 |
2001年 | 62篇 |
2000年 | 63篇 |
1999年 | 48篇 |
1998年 | 45篇 |
1997年 | 40篇 |
1996年 | 48篇 |
1995年 | 28篇 |
1994年 | 24篇 |
1993年 | 34篇 |
1992年 | 31篇 |
1991年 | 36篇 |
1990年 | 44篇 |
1989年 | 47篇 |
1988年 | 45篇 |
1987年 | 42篇 |
1986年 | 29篇 |
1985年 | 34篇 |
1984年 | 24篇 |
1983年 | 32篇 |
1982年 | 27篇 |
1981年 | 18篇 |
1980年 | 19篇 |
1979年 | 14篇 |
1978年 | 9篇 |
1977年 | 17篇 |
1976年 | 27篇 |
1975年 | 13篇 |
1974年 | 11篇 |
1970年 | 11篇 |
1968年 | 11篇 |
排序方式: 共有2125条查询结果,搜索用时 31 毫秒
1.
M.Y. Mommaerts G. Van Hemelen K. Sanders J. Vander Sloten K. Van Brussel J.V.S. Abeloos C.A.S. De Clercq L.F. Neyt 《The British journal of oral & maxillofacial surgery》1997,35(6):398-400
Clinical experience in genioplasty has shown that high labial incisions heal with fewer scar bands than conventional deep labial incisions. In a prospective randomized trial, we compared 18 high labial curvilinear incisions with 27 high labial W-shaped (‘royal’) incisions for access and visibility during chin osteotomy. Both incisions were 3 cm wide. Maximal incision lengthening between two skin hooks was recorded with a ruler before closure, and there was no significant difference between the two. The maximum wound area between three skin hooks was photographed and computed, and showed a mean difference of 188.75 mm2 (t-test, P < 0.001), which corroborated the clinical findings that access and visibility were superior in the W-shaped incision group. Complications were few in both groups. We now use the high labial royal incision about 3.5 cm wide, with 90° limb angle for complicated chin osteotomies and ostectomies. A smaller curvilinear high labial incision is used for simple advancement osteotomies. 相似文献
2.
Duyck J Van Oosterwyck H Vander Sloten J De Cooman M Puers R Naert I 《Clinical oral investigations》1999,3(4):201-207
This study was designed to gain insight into the influence of the attachment system on the loading conditions of oral implants supporting a mandibular overdenture on two implants. Five patients were selected and were provided with two implants in the canine area of the mandible (Brånemark System). All patients received a new mandibular overdenture that could be mounted on an ovoid-shaped bar (Dolder, C&;M): (a) with and (b) without bilateral extensions and (c) on ball-attachments (Nobel Biocare). Using three strain gauges attached to the outer surface of the 5.5-mm standard abutments, the axial forces and bending moments on both supporting implants could be quantified. Load registrations were made during application of 50 N on seven predetermined positions along the occlusal surface of the prosthesis and during maximal biting in maximal occlusion (clenching). The results revealed no differences in induced axial force for the various anchorage devices, unlike the differences in bending moment. Although there is a tendency for better axial load sharing with bars and better sharing of bending moments with ball attachments, these differences were not significant. 相似文献
3.
BACKGROUND: Critical factors for the establishment of osseointegration are the implant surface microtopography and the local mechanical environment. The present study evaluated the bone response around a turned (T) and a roughened (R) implant for either an unloaded or a well-controlled loaded situation. METHODS: Bone chambers were installed in the tibia of 20 rabbits. In each of the chambers, two identical displacement-controlled loading experiments were performed: 30 microm for 400 cycles at 1 Hz, three times a week for 9 weeks versus 0-microm implant displacement. A linear mixed model and a logistic mixed model with alpha = 5% were set to study the significant effect of the surface texture on the peri-implant bone response in the unloaded (T-0 microm versus R-0 microm) and the loaded (T-30 microm versus R-30 microm) mode. RESULTS: Results indicated no microtopographic dependence of the bone response further away from the implant in unloaded and loaded conditions. For a load-free implant, osseointegration seemed to occur with a higher incidence at a roughened compared to a turned implant surface. In the presence of loading, the topographic dependency of the osteogenic activity at the interface was overruled by the loading-related bone response, revealing no significant differences in osseointegration incidence between T and R. CONCLUSION: A predominant effect of the interfacial mechanical environment over the implant surface characteristics on the differentiating cell population is suggested. 相似文献
4.
K J Kelly P N Manson C A Vander Kolk B L Markowitz C M Dunham T O Rumley W A Crawley 《The Journal of craniofacial surgery》1990,1(4):168-178
The types of midfacial fractures and their complexity were evaluated in admissions to the Maryland Institute of Emergency Medical Service Systems (MIEMSS) during the years of 1984 to 1988. Two hundred and sixty-eight LeFort fractures were treated and followed (3.2 percent of admissions). One half (50 percent) had skull fractures and 40 patients (15 percent) had LeFort, skull and mandibular fractures. Isolated nasoethmoidal fractures were observed in 176 patients and in 107 patients (39 percent) of patients with LeFort fractures. Isolated mandibular fractures were observed in 321 patients and in 104 patients with LeFort fractures (39 percent). Eleven percent of patients had midfacial, nasoethmoidal and frontal sinus fractures. Six percent of patients had midfacial, frontal bone, frontal sinus and nasoethmoidal fractures (Cranial Base Crush Syndrome). Twenty two percent of patients had LeFort and frontal sinus fractures. Reconstruction of multiple area injuries is simplified by a highly organized treatment sequence that conceptualizes the face in two groups of two units. Each unit is divided into sections, and each section is assembled in three dimensions. Sections are integrated into units and units into a single reconstruction. Conceptually, in each unit, facial width must first be controlled by orientation from cranial base landmarks. Projection is then (and often reciprocally with width) established. Finally, facial length is set both in individual units and in the upper and lower face. Soft tissue is considered the "fourth dimension" of facial reconstruction. Bone reconstruction should be completed as early as possible to minimize soft tissue shrinkage, stiffness and scarring of soft tissues in nonantomic positions.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
5.
Spring-mediated mandibular distraction osteogenesis 总被引:4,自引:0,他引:4
Mofid MM Inoue N Tufaro AP Vander Kolk CA Manson PN 《The Journal of craniofacial surgery》2003,14(5):756-762
Successful performance of distraction osteogenesis requires rigorous patient compliance with a daily activation regimen of a percutaneous screw. Previous clinical studies have found that failure of patient compliance with this regimen is the most common complication leading to technical failure of the distraction process. The authors have developed an internalized spring-mediated device for mandibular distraction osteogenesis that can potentially abrogate the risks associated with patient compliance by allowing for automated distraction across an osteotomy. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A segment of nickel-titanium shape memory alloy reinforced at both ends with a pinball was fashioned into an inferiorly based arc and secured to the mandible with stainless steel wire. On postoperative day 12, spring activation commenced by cutting a wire binding the two pinballs to one another. Animals were observed for 6 weeks before they were killed. Radiographic studies and decalcified histologic analysis were performed on extracted mandibles. Temperature- and displacement-dependent properties of the shape memory alloy were also examined. Five animals were excluded from the study due to infection, nonunion, or device failure. A mean distraction of 1.2 mm in the distracted hemimandible relative to the nonoperated hemimandible was found (P <.001, two-tailed paired t test). The maximum distraction achieved in an experimental specimen using the spring distractor was 3.7 mm. There were no other histologic or radiographic differences found between study specimens and specimens subjected to traditional distraction methods. Biomechanical testing of the shape memory alloy revealed a temperature-dependent increase in force at body temperature compared with room temperature and a reduction in force with increased displacement of the spring. This study demonstrates the feasibility of spring-mediated distraction osteogenesis across an osteotomy. As the field of distraction osteogenesis matures, the next level of sophistication in the clinical development of devices will incorporate technology that permits fully internalized and automated distraction to occur. 相似文献
6.
7.
Ohad Ronen K. Thomas Robbins Kerry D. Olsen Ashok R. Shaha Gregory W. Randolph Iain J. Nixon Mark E. Zafereo Dana M. Hartl Luiz P. Kowalski Juan P. Rodrigo Andrs Coca‐Pelaz Antti A. Mkitie Vincent Vander Poorten Alvaro Sanabria Peter Angelos Alessandra Rinaldo Alfio Ferlito 《Head & neck》2020,42(10):3061-3071
Recent modifications in the management of well‐differentiated thyroid cancer have resulted in significant alterations in clinical approach. Utilizing a series of preoperative and postoperative risk factors involving both the patient and the disease pathology, we offer the term “staged thyroidectomy” to help organize these risk factors for patients and the endocrine team to optimize management. This approach is intended to incorporate our latest nuanced understanding of certain endocrine pathology and may serve to optimize patient outcomes. 相似文献
8.
David A. Meekins Madushi Raththagala Satrio Husodo Cory J. White Hou-Fu Guo Oliver K?tting Craig W. Vander Kooi Matthew S. Gentry 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(20):7272-7277
Plants use the insoluble polyglucan starch as their primary glucose storage molecule. Reversible phosphorylation, at the C6 and C3 positions of glucose moieties, is the only known natural modification of starch and is the key regulatory mechanism controlling its diurnal breakdown in plant leaves. The glucan phosphatase Starch Excess4 (SEX4) is a position-specific starch phosphatase that is essential for reversible starch phosphorylation; its absence leads to a dramatic accumulation of starch in Arabidopsis, but the basis for its function is unknown. Here we describe the crystal structure of SEX4 bound to maltoheptaose and phosphate to a resolution of 1.65 Å. SEX4 binds maltoheptaose via a continuous binding pocket and active site that spans both the carbohydrate-binding module (CBM) and the dual-specificity phosphatase (DSP) domain. This extended interface is composed of aromatic and hydrophilic residues that form a specific glucan-interacting platform. SEX4 contains a uniquely adapted DSP active site that accommodates a glucan polymer and is responsible for positioning maltoheptaose in a C6-specific orientation. We identified two DSP domain residues that are responsible for SEX4 site-specific activity and, using these insights, we engineered a SEX4 double mutant that completely reversed specificity from the C6 to the C3 position. Our data demonstrate that the two domains act in consort, with the CBM primarily responsible for engaging glucan chains, whereas the DSP integrates them in the catalytic site for position-specific dephosphorylation. These data provide important insights into the structural basis of glucan phosphatase site-specific activity and open new avenues for their biotechnological utilization.Starch is the primary carbohydrate storage molecule in plants and is an essential constituent of human and animal diets. Starch granules are composed of the glucose homopolymers amylose (10–25%) and amylopectin (75–90%) (1, 2). Amylose is a linear molecule formed from α-1,4-glycosidic–linked chains, whereas amylopectin is formed from α-1,4-glycosidic–linked chains with α-1,6-glycosidic–linked branches (3, 4). Adjacent amylopectin chains interact to form double helices that cause starch granules to be water insoluble, which is an essential feature for its function as a glucose storage molecule (1, 3, 5). However, the outer granular surface of transitory starch must be solubilized during nonphotosynthetic periods so that glycolytic enzymes can access and degrade starch glucans and meet the metabolic needs of the plant (6, 7). Plants regulate the solubility of the starch granular surface via reversible starch phosphorylation that results in a cyclic degradative process: phosphorylation by dikinases, degradation by starch hydrolyzing amylases, and dephosphorylation by phosphatases (1, 8–11). Phosphorylation of amylopectin chains causes helical unwinding and local solubilization of the outer starch granule (12–14). The local solubilization and helix unwinding permits degradation of surface, linear α-1,4 glucan chains by β-amylase, which sequentially removes maltosyl units from the nonreducing end (1, 8, 15). Although glucan phosphorylation of the starch surface is necessary for degradation, the removal of these phosphate groups is required because β-amylase is unable to degrade past the phosphate (6, 15–17). Therefore, glucan phosphatases must release phosphate from starch to reset the degradation cycle, allowing processive starch degradation (8, 16).Recent studies have established that plants use a two-enzyme system for both starch phosphorylation and dephosphorylation. α-Glucan water dikinase phosphorylates the hydroxyl group of starch glucose at the C6 position. This event triggers phosphorylation of the hydroxyl group at the C3 position by phosphoglucan water dikinase (18–21). Similarly, two glucan phosphatases release phosphate from starch. Starch Excess4 (SEX4) preferentially dephosphorylates the C6 position of starch glucose and Like Sex Four2 (LSF2) exclusively dephosphorylates the C3 position (22–26). SEX4 activity is essential for starch catabolism and its mutation in Arabidopsis leads to an excess of leaf starch, a decrease in plant growth, and an accumulation of soluble phosphoglucans produced by the activity of α-amylase 3 and the debranching enzyme isoamylase 3 (16, 25, 27). Conversely, lsf2 mutant Arabidopsis plants display normal levels of leaf starch and plant growth, but the starch contains increased levels of C3-phosphate (22). The difference in plant vitality between sex4 and lsf2 mutants is likely due to SEX4 possessing some compensatory C3-position phosphatase activity (22). Cumulatively, the process of reversible phosphorylation requires the concerted activity of dikinases and phosphatases with SEX4 activity being essential for normal patterns of starch metabolism and plant growth.Glucan phosphatases are members of the protein tyrosine phosphatase (PTP) superfamily characterized by a conserved Cx5R catalytic motif (24, 28, 29). The glucan phosphatases belong to a heterogeneous subset of PTPs called dual-specificity phosphatases (DSPs), with some DSPs dephosphorylating p-Tyr and p-Ser/Thr residues of proteinaceous substrates and other DSPs dephosphorylating lipids, nucleic acids, or glucans (30–32). In addition to SEX4 and LSF2, a glucan phosphatase called laforin has been identified that dephosphorylates glycogen and influences its solubility in vertebrates (24, 33, 34). Loss of laforin function in humans results in a fatal, neurodegenerative epilepsy called Lafora disease (35–37). Due to their critical function in complex carbohydrate metabolism, understanding the structural basis of glucan phosphatase activity is of particular interest. Toward this goal, we previously determined the ligand-free structure of SEX4 and identified an extensive interdomain interface between its DSP domain and carbohydrate-binding module (CBM) that is maintained in part by a previously unrecognized C-terminal (CT) motif (38). However, the structural mechanism for domain coupling, glucan interaction, and specific C6 dephosphorylation in SEX4 activity is unclear.Starch granule solubilization depends on phosphorylation of starch glucose on the hydroxyl group at both the C6 and C3 positions (6, 13). These phosphorylation events are critical for normal transitory starch degradation, but also directly impact the melting temperature, viscosity, and hydration of starch in industrial settings (39, 40). Developing a means to manipulate starch phosphorylation patterns via enzymatic modification is relevant to agricultural and industrial applications that use starch as a feedstock (9, 12, 14, 41). Therefore, understanding the basis for the site specificity of glucan phosphatases is of particular interest. We recently determined the structure of LSF2 with a glucan bound in a C3-specific orientation and identified unique noncatalytic surface-binding sites (SBSs) not found in other glucan phosphatases (26). SEX4 lacks SBSs and preferentially dephosphorylates the C6 position. The present study was designed to define the fundamental basis for SEX4 substrate binding and understand preferential C6-position specificity in SEX4.Herein, we elucidate the structural mechanism of SEX4-specific activity by determining the structure of SEX4 bound to the phosphoglucan products maltoheptaose and phosphate. SEX4 engages glucan chains via an extended interface of aromatic and hydrophilic residues that spans the CBM and DSP domains. Moreover, the SEX4 CBM is primarily responsible for glucan binding whereas the SEX4 DSP active site is uniquely adapted to engage the phosphoglucan substrate, positioning it in a C6-specific orientation. Structure-guided mutagenesis of DSP active-site residues resulted in a complete reversal from C6 to preferential C3 dephosphorylation by SEX4. Cumulatively, this study establishes the molecular basis for both SEX4 substrate engagement and SEX4 specificity and provides a method for engineering glucan phosphatase activity with modified site specificity. 相似文献
9.
Roberto S. Pessoa Fábio J.B. Bezerra Ravel M. Sousa Jos Vander Sloten Marcio Zaffalon Casati Siegfried V.N. Jaecques 《Journal of periodontology》2014,85(9):1161-1171
Background: It is not yet well understood to what extent different implant–abutment mismatch sizes and implant–abutment connection types may influence the peri‐implant biomechanical environment of implants in different clinical situations. Methods: Computed tomography–based finite element models comprising a maxillary central incisor socket and 4.5 × 13 mm outer‐diameter implants with external and internal hex connection types were constructed. The abutments were designed with diameters of 3.5 mm (platform switching [PS] with 1 mm of diametral mismatch [PS ? 1]), 4.0 mm (PS with 0.5 mm of diametral mismatch [PS ? 0.5]), and 4.5 mm (conventional matching implant–abutment design [CD]). Analysis of variance at the 95% confidence interval was used to evaluate peak equivalent strain (EQV strain) in the bone, bone volume affected by a strain >4,000 με (EQV strain >4,000 με), the peak von Mises stress (EQV stress) in abutment screw, and the bone–implant relative displacement. Results: Similar bone strain levels (EQV strain and EQV strain >4,000 με) were encountered in PS ? 1, PS ? 0.5, and CD models for immediately placed implants, independent of the connection type. For immediately loaded implants, slightly smaller peak EQV strain and EQV strain >4,000 με were found for PS ? 1. However, for both connection types in osseointegrated models, the higher the mismatch size, the lesser the amount of strain found. Conclusions: The increase in mismatch size of PS configuration results in a significant decrease of strain levels in bone for osseointegrated implants, principally for external hex connections. No significant effect of PS could be noted in immediately placed implants. 相似文献
10.
Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation 总被引:7,自引:25,他引:7 下载免费PDF全文
E Heber-Katz RH Schwartz LA Matis C Hannum T Fairwell E Appella D Hansburg 《The Journal of experimental medicine》1982,155(4):1086-1099