全文获取类型
收费全文 | 53542篇 |
免费 | 5102篇 |
国内免费 | 4093篇 |
出版年
2023年 | 876篇 |
2022年 | 1061篇 |
2021年 | 1312篇 |
2020年 | 1422篇 |
2019年 | 2005篇 |
2018年 | 1837篇 |
2017年 | 1548篇 |
2016年 | 1426篇 |
2015年 | 1392篇 |
2014年 | 2683篇 |
2013年 | 3404篇 |
2012年 | 2043篇 |
2011年 | 2555篇 |
2010年 | 1873篇 |
2009年 | 2419篇 |
2008年 | 2557篇 |
2007年 | 2838篇 |
2006年 | 2540篇 |
2005年 | 2096篇 |
2004年 | 1787篇 |
2003年 | 1748篇 |
2002年 | 1532篇 |
2001年 | 1278篇 |
2000年 | 1073篇 |
1999年 | 926篇 |
1998年 | 825篇 |
1997年 | 822篇 |
1996年 | 816篇 |
1995年 | 827篇 |
1994年 | 829篇 |
1993年 | 744篇 |
1992年 | 714篇 |
1991年 | 711篇 |
1990年 | 564篇 |
1989年 | 569篇 |
1988年 | 517篇 |
1987年 | 477篇 |
1986年 | 471篇 |
1985年 | 740篇 |
1984年 | 996篇 |
1983年 | 811篇 |
1982年 | 851篇 |
1981年 | 675篇 |
1980年 | 678篇 |
1979年 | 601篇 |
1978年 | 448篇 |
1977年 | 415篇 |
1976年 | 377篇 |
1974年 | 248篇 |
1973年 | 267篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Shuichi Nagashima Hiroaki Yagyu Ryuichi Tozawa Fumiko Tazoe Manabu Takahashi Tetsuya Kitamine Daisuke Yamamuro Kent Sakai Motohiro Sekiya Hiroaki Okazaki Jun-ichi Osuga Akira Honda Shun Ishibashi 《Journal of lipid research》2015,56(5):998-1005
Squalene synthase (SS) catalyzes the biosynthesis of squalene, the first specific intermediate in the cholesterol biosynthetic pathway. To test the feasibility of lowering plasma cholesterol by inhibiting hepatic SS, we generated mice in which SS is specifically knocked out in the liver (L-SSKO) using Cre-loxP technology. Hepatic SS activity of L-SSKO mice was reduced by >90%. In addition, cholesterol biosynthesis in the liver slices was almost eliminated. Although the hepatic squalene contents were markedly reduced in L-SSKO mice, the hepatic contents of cholesterol and its precursors distal to squalene were indistinguishable from those of control mice, indicating the presence of sufficient centripetal flow of cholesterol and/or its precursors from the extrahepatic tissues. L-SSKO mice showed a transient liver dysfunction with moderate hepatomegaly presumably secondary to increased farnesol production. In a fed state, the plasma total cholesterol and triglyceride were significantly reduced in L-SSKO mice, primarily owing to reduced hepatic VLDL secretion. In a fasted state, the hypolipidemic effect was lost. mRNA expression of liver X receptor α target genes was reduced, while that of sterol-regulatory element binding protein 2 target genes was increased. In conclusion, liver-specific ablation of SS inhibits hepatic cholesterol biosynthesis and induces hypolipidemia without increasing significant mortality. 相似文献
2.
P. Bourke D. Ziuzina L. Han P.J. Cullen B.F. Gilmore 《Journal of applied microbiology》2017,123(2):308-324
There is a diverse range of microbiological challenges facing the food, healthcare and clinical sectors. The increasing and pervasive resistance to broad‐spectrum antibiotics and health‐related concerns with many biocidal agents drives research for novel and complementary antimicrobial approaches. Biofilms display increased mechanical and antimicrobial stability and are the subject of extensive research. Cold plasmas (CP) have rapidly evolved as a technology for microbial decontamination, wound healing and cancer treatment, owing to the chemical and bio‐active radicals generated known collectively as reactive oxygen and nitrogen species. This review outlines the basics of CP technology and discusses the interactions with a range of microbiological targets. Advances in mechanistic insights are presented and applications to food and clinical issues are discussed. The possibility of tailoring CP to control specific microbiological challenges is apparent. This review focuses on microbiological issues in relation to food‐ and healthcare‐associated human infections, the role of CP in their elimination and the current status of plasma mechanisms of action. 相似文献
3.
C. Lawrence Kien Dwight E. Matthews Matthew E. Poynter Janice Y. Bunn Naomi K. Fukagawa Karen I. Crain David B. Ebenstein Emily K. Tarleton Robert D. Stevens Timothy R. Koves Deborah M. Muoio 《Journal of lipid research》2015,56(9):1795-1807
Palmitic acid (PA) is associated with higher blood concentrations of medium-chain acylcarnitines (MCACs), and we hypothesized that PA may inhibit progression of FA β-oxidation. Using a cross-over design, 17 adults were fed high PA (HPA) and low PA/high oleic acid (HOA) diets, each for 3 weeks. The [1-13C]PA and [13-13C]PA tracers were administered with food in random order with each diet, and we assessed PA oxidation (PA OX) and serum AC concentration to determine whether a higher PA intake promoted incomplete PA OX. Dietary PA was completely oxidized during the HOA diet, but only about 40% was oxidized during the HPA diet. The [13-13C]PA/[1-13C]PA ratio of PA OX had an approximate value of 1.0 for either diet, but the ratio of the serum concentrations of MCACs to long-chain ACs (LCACs) was significantly higher during the HPA diet. Thus, direct measurement of PA OX did not confirm that the HPA diet caused incomplete PA OX, despite the modest, but statistically significant, increase in the ratio of MCACs to LCACs in blood. 相似文献
4.
5.
Rapid prioritization of alien plants for eradication based on climatic suitability and eradication feasibility 下载免费PDF全文
Identifying which introduced species have the greatest potential for establishment, spread and impact is critical for prioritizing pre‐ and post‐border control. Using species distribution modelling and existing species locations we assessed the establishment risk based on the climatic suitability areas of 25 plant species listed as eradication targets under South African regulations. To improve confidence, three bioclimatic models were used to predict the potential distribution of each species. This information was combined with the number of localities and the “eradication feasibility syndromes” in a scoring‐categorical system to rank the species. Three management groups were identified. Group “A” includes species with medium‐high establishment risk and higher likelihood to be eradicated, these species should be a priority for eradication. Group “B” includes species with a medium‐low establishment risk but given the low number of known population and the species characteristics, eradication is likely to be feasible. Finally species in group “C” scored a medium‐high establishment risk but the eradication would be difficult due to the high number of known localities. This ranking provides a rapid method to prioritize the management towards the eradication of new potential invasive plant species in the country combining the establishment risk, known number of localities and the inferred eradication success. 相似文献
6.
7.
Atypical surface behavior of ceramides with nonhydroxy and 2-hydroxy very long-chain (C28–C32) PUFAs
Daniel A. Peñalva Gerardo M. Oresti Fernando Dupuy Silvia S. Antollini Bruno Maggio Marta I. Aveldaño María L. Fanani 《生物化学与生物物理学报:生物膜》2014
Unique species of ceramide (Cer) with very-long-chain polyunsaturated fatty acid (VLCPUFA), mainly 28–32 carbon atoms, 4–5 double bonds, in nonhydroxy and 2-hydroxy forms (n-V Cer and h-V Cer, respectively), are generated in rat spermatozoa from the corresponding sphingomyelins during the acrosomal reaction. The aim of this study was to determine the properties of these sperm-distinctive ceramides in Langmuir monolayers. Individual Cer species were isolated by HPLC and subjected to analysis of surface pressure, surface potential, and Brewster angle microscopy (BAM) as a function of molecular packing. In comparison with known species of Cer, n-V Cer and h-V Cer species showed much larger mean molecular areas and increased molecular dipole moments in liquid expanded phases, which suggest bending and partial hydration of the double bonded portion of the VLCPUFA. The presence of the 2-hydoxyl group induced a closer molecular packing in h-V Cer than in their chain-matched n-V Cer. In addition, all these Cer species showed liquid-expanded to liquid-condensed transitions at room temperature. Existence of domain segregation was confirmed by BAM. Additionally, thermodynamic analysis suggests a phase transition close to the physiological temperature for VLCPUFA-Cers if organized as bulk dispersions. 相似文献
8.
Mitochondrial hexokinase (HK) and creatine kinase (CK) known to form complexes with a voltage dependent anion channel (VDAC) have been reported to increase cell death resistance under hypoxia/anoxia. In this work we propose a new, non-Mitchell mechanism of generation of the inner and outer membrane potentials at anaerobic conditions. The driving force is provided by the Gibbs free energy of the HK and CK reactions associated with the VDAC–HK and the ANT (adenine nucleotide translocator)–CK–VDAC complexes, respectively, both functioning as voltage generators. In the absence of oxygen, the cytosolic creatine phosphate can be directly used by the ANT–CK–VDAC contact sites to produce ATP from ADP in the mitochondrial matrix. After that, ATP released through the fraction of unbound ANTs in exchange for ADP is used in the mitochondrial intermembrane space by the outer membrane VDAC–HK electrogenic complexes to convert cytosolic glucose into glucose-6-phosphate. A simple computational model based on the application of Ohm's law to an equivalent electrical circuit showed a possibility of generation of the inner membrane potential up to − 160 mV, under certain conditions, and of relatively high outer membrane potential without wasting of ATP that normally leads to cell death. The calculated membrane potentials depended on the restriction of ATP/ADP diffusion in narrow cristae and through the cristae junctions. We suggest that high inner membrane potential and calcium extrusion from the mitochondrial intermembrane space by generated positive outer membrane potential prevent mitochondrial permeability transition, thus allowing the maintenance of mitochondrial integrity and cell survival in the absence of oxygen. 相似文献
9.
目的:探讨踝肱指数(ABI)与糖尿病周围神经病变及中医证候积分的相关性。方法:选取我院内分泌科收治辩证以气阴两虚
为证型的糖尿病患者66 例,根据踝肱指数实验将患者分为ABI降低组(0.9>ABI>0.5)和ABI 正常组(1.4>ABI>0.9)。记录患者神
经病变症状尼龙丝检查以及中医症候评分,分析ABI与糖尿病周围神经病变及中医证候积分的相关性。结果:ABI降低组的糖尿
病周围神经病变的患病率高于ABI正常组(P<0.05)。ABI 降低组发麻、针刺感症状的发生率高于ABI 正常组,且有统计学差异
(P<0.05)。ABI降低组10 g尼龙丝检查异常者多于ABI正常组,差异显著(P<0.05)。ABI降低组的感觉振动阈值高于ABI正常组
(P<0.05)。ABI数值与中医证候积分呈负向直线相关(P<0.05)。结论:糖尿病患者ABI数值与糖尿病周围神经病变和中医证候积
分具有相关性。 相似文献
10.
目的:探讨和比较不同手术术式治疗涉及桡骨远端的骨肉瘤的手术适应症选择,临床疗效和安全性。方法:将2005 年-2014
年我院收治的涉及到桡骨远端并进行外科手术治疗的骨巨细胞瘤患者共88 例进行回顾性分析。根据影像学Campanacci分级,主
要手术方法分为以下三种,分别为:A组:微波天线高温原位灭活,自体髂骨,异体骨粒符合骨水泥重建修复术;B:瘤骨切除并腓
骨移植术;C:瘤骨刮除灭活并原位植骨术。结合详实的随访资料对两组患者在术后的复发率,腕关节功能(Enneking)等情况给予
分析和评价。结果:A 组复发率为10.87 %,腕关节功能MSTS93 功能评分为26.32± 2.92分。B 组复发率为0,腕关节术后的
MSTS93 功能评分为22.85± 4.16 分。C 组复发率为30.24 %。腕关节术后的MSTS93 功能评分为26.97± 2.84 分。三组相比,A、
B 与C 组在复发率中有明显统计学差异(P<0.05),A 组、C组的术后功能评分明显优于B 组(P<0.05),但两组之间无统计学差异
(P>0.05)。A 组中有1 例切口表层感染,B 组中有2 例皮肤感染,均经加强换药后治愈。结论:瘤段切除手术能够有效的降低复发
率,但局部功能恢复较差,容易出现切口感染等并发症。微波灭活手术可以有效的杀灭肿瘤组织并保证良好的功能性,但复发率
相对较高。在临床工作中应根据患者具体病情和需要给予针对性的手术方案。 相似文献