首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   263494篇
  免费   24517篇
  国内免费   20601篇
耳鼻咽喉   2015篇
儿科学   2305篇
妇产科学   3005篇
基础医学   32627篇
口腔科学   4274篇
临床医学   37885篇
内科学   38494篇
皮肤病学   2405篇
神经病学   14875篇
特种医学   9538篇
外国民族医学   198篇
外科学   25082篇
综合类   44080篇
现状与发展   74篇
一般理论   27篇
预防医学   15854篇
眼科学   8180篇
药学   28207篇
  299篇
中国医学   15602篇
肿瘤学   23586篇
  2024年   937篇
  2023年   4375篇
  2022年   11345篇
  2021年   14082篇
  2020年   10641篇
  2019年   9297篇
  2018年   9668篇
  2017年   8510篇
  2016年   8094篇
  2015年   12179篇
  2014年   14957篇
  2013年   12522篇
  2012年   18720篇
  2011年   21529篇
  2010年   13036篇
  2009年   10068篇
  2008年   13338篇
  2007年   13373篇
  2006年   13599篇
  2005年   13858篇
  2004年   8203篇
  2003年   7610篇
  2002年   6378篇
  2001年   5698篇
  2000年   6422篇
  1999年   7179篇
  1998年   4745篇
  1997年   4769篇
  1996年   3680篇
  1995年   3515篇
  1994年   2898篇
  1993年   1964篇
  1992年   2213篇
  1991年   1844篇
  1990年   1571篇
  1989年   1334篇
  1988年   1133篇
  1987年   992篇
  1986年   748篇
  1985年   608篇
  1984年   348篇
  1983年   214篇
  1982年   115篇
  1981年   126篇
  1980年   83篇
  1979年   90篇
  1977年   2篇
  1965年   1篇
  1962年   1篇
排序方式: 共有10000条查询结果,搜索用时 18 毫秒
961.
BackgroundBecause trends in the epidemiology and burden of gastroesophageal reflux disease (GERD) are changing, reinvestigating the geographical differences and trend changes is essential. Here we evaluated the latest epidemiologic patterns and trends for GERD, using data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.MethodsAnnual case numbers, age-standardized rates of prevalence, incidence, and years of life lived with disability (YLDs), and their estimated annual percentage changes (EAPCs) for GERD between 1990 and 2019 were derived from the GBD 2019 study. Association between GERD burden and socio-demographic index (SDI) was also investigated.ResultsIn 2019, there were 783.95 million cases of GERD globally. Between 1990 and 2019, the total number of prevalent cases, incident cases, and YLDs increased by 77.53%, 74.79%, and 77.19%, respectively. The global age-standardized incidence rate (ASIR) and age-standardized YLD rate (ASYR) increased during this period (EAPC = 0.06 and 0.05, respectively). Tropical Latin America and East Asia had the highest and lowest age-standardiZed prevalence rate (ASPR), ASIR, and ASYR in 2019, respectively. From 1990 to 2019, prevalent cases, incident cases, YLDs, and their corresponding age-standardized rates of GERD were higher in females than males in all years. Higher SDI was associated with lower ASPR, ASIR, and ASYR of GERD in 2019.ConclusionsGERD will continue to be a major public health burden due to increasing numbers of prevalent cases, incident cases, and YLDs. In order to tackle this troublesome disease, it is crucial to understand the changes in both global and regional trends in epidemiology and the burden for policymakers and other stakeholders.

Key messages

  • This is the most updated estimate on GERD epidemiology globally, including 204 countries, some of which were not assessed before.
  • The overall burden of GERD continued to worsen with the prevalent cases increasing by 77.53% from 441.57 million in 1990 to 783.95 million in 2019.
  • GERD is likely to remain a common reason for consultation in primary care, and our data may allow for health service provision planning.
  相似文献   
962.
超声诊断颌下腺炎的临床应用   总被引:1,自引:0,他引:1  
目的探讨超声诊断颌下腺炎的临床应用价值。方法选取101例经手术证实的颌下腺炎的超声图像,分析颌下腺的大小、形态、内部回声及彩色血流情况。结果101例颌下腺炎中,急性炎症2例,慢性炎症99例,超声与手术病理结果符合率为98%。结论超声对颌下腺炎的诊断准确率较高,并能与颌下区占位性病变相鉴别。  相似文献   
963.
目的探讨心力衰竭对门静脉频谱形态的影响,摸索超声检查评价心功能的新途径。方法选取临床Ⅰ~Ⅲ度心力衰竭患者60例,按心衰竭程度分组,每组各20例;健康对照组20例。排除肝脏及门静脉、下腔静脉病变。经右侧肋间及剑突下探查门静脉,在取得门静脉清晰二维切面图像后,记录1~3个呼吸周期中的门静脉频谱,观察频谱形态,记录各组不同门静脉频谱形态的例数,所获资料采用统计软件SPSS11.0处理。结果健康对照组门静脉频谱均表现为单向连续频谱,各心力衰竭组出现不同程度的门静脉收缩末期反向血流,Ⅲ度心力衰竭组门静脉频谱多出现恒定的收缩末期反向血流。结论心力衰竭可导致门静脉频谱形态异常,观察门静脉频谱形态,可作为判断心力衰竭程度的辅助依据。  相似文献   
964.
A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.

A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.

Since the well-known failure of using racemic thalidomide, attention has been paid to the manufacture of optically pure compounds as effective components in pharmaceuticals and agrochemicals. Asymmetric hydrogenation of ketones, especially heteroaromatic ketones, has emerged as a popular facile route to approach enantiopure secondary alcohols as essential intermediates for the construction of biologically active molecules.1–4 Knowles et al.5 pioneered the production of enantioenriched chiral compounds in 1968, and Noyori and co-workers6–8 laid the cornerstone of asymmetric hydrogenation in 1990s. Subsequently, numerous catalytic systems have been developed. Ru-BICP-chiral diamine-KOH was developed and proved to be effective for asymmetric hydrogenation of aromatic ketones by Xumu Zhang.9 Cheng-yi Chen reported asymmetric hydrogenation of ketone using trans-RuCl2[(R)-xylbinap][(R)-daipen] and afforded secondary alcohol in 92–99% ee.10 Mark J. Burk and Antonio Zanotti-Gerosa disclosed Phanephos-ruthenium-diamine complexes catalyzing the asymmetric hydrogenation of aromatic and heteroaromatic ketones with high activity and excellent enantioselectivity.11 Qi-Lin Zhou et al. designed and synthesized chiral spiro diphosphines as a new chiral scaffold applied in the asymmetric hydrogenation of simple ketones with extremely high activity and up to 99.5% ee.12–15 Similarly, Kitamura and co-workers have developed a set of tridentate binan-Py-PPh2 ligands for the asymmetric hydrogenation of ketones affording excellent results.16 Recently, chiral diphosphines and tridentate ligands based on ferrocene have been developed for the asymmetric hydrogenation of carbonyl compound with a remarkable degree of success.17–21 Despite many ligands for asymmetric hydrogenation of ketones have been reported, expensive reagent and multistep complicated reactions were employed to synthesize most of them.22–24 In light of increasing industrial demand, easily obtained, cheap and practical chiral ligands are still highly desirable. In addition to chiral ligands, the selection of metals was essential for asymmetric hydrogenation.25–27 Although Mn,28–30 Fe,31–34 Co,35–37 Ni38,39 and Cu40,41 metals were proved to be effective for asymmetric hydrogenation in recent years, Rh,42–44 Ir45,46 and especially Ru remained the most preferred metals. Ruthenium47–51 was chosen owing to its superior performances in terms of low price, selectivity and activity. Takeshi Ohkuma,52 Hanmin Huang53,54 and Johannes G. de Vries55 all successfully used ruthenium catalysts for asymmetric hydrogenation of ketones. Admittedly, there is a continuing interest in the development of cheaper, simpler and more efficient catalysts for the asymmetric hydrogenation of ketones under mild conditions to access corresponding secondary alcohols. Recently, we developed new NNP chiral ligands derived from cinchona alkaloid for the asymmetric hydrogenation of various ketones in extremely excellent results using a iridium catalytic system.56 Prompted by these encouraging results, we were interested in exploring a ruthenium-catalyzed asymmetric hydrogenation of ketones with NNP chiral ligands derived from cinchona alkaloid. Here, we showed that changing from iridium to ruthenium, with the same simple synthetic ligands, delivered a catalyst catalyzed asymmetric hydrogenation of ketones to give the industrially important chiral alcohols with up to 99.9% ee. Although the catalytic activity of ruthenium catalyst was not as high as that of the iridium catalyst, the enantioselectivity could be maintained, and even showed higher enantioselectivity in the hydrogenation of some substrates.Chiral tridentate ligand NNP (L1–L10) were synthesized and characterized as reported in our previous publication. With tridentate ligands in hand, we began to evaluate the catalytic performance in benzylidene-bis(tricyclohexylphosphine) dichlororuthenium-catalyzed asymmetric hydrogenation of acetophenone employed as a standard substrate (Fig. 2). MeOH was found to be a better one as the conversion and enantioselectivity were 99.9% and 98.2%, respectively. Bases screening showed that Ba(OH)2 was superior to the others, giving >99.9% conversion and 98.8% ee in the present catalytic system (Fig. 1). Ligand screening revealed that the configuration of chiral centers of cinchona alkaloids of the ligand markedly affected the catalytic performance. NNP ligands derived from cinchonine and quinidine appeared to benefit both the reaction rate and enantioselectivity, while those derived from cinchonidine and quinine had the opposite effect. Further, different NNP ligands that bearing different substituents on the phenyl rings were evaluated. Similar to our previous research, ligands with electron-withdonating substituents showed better catalytic performance than those with electron-withdrawing substituents. However, it was noted that the more electron-withdonating substituents furnished lower activity but same enantioselectivity. The optimal ligand L5 derived from quinidine with one methoxy group on benzene ring provided the corresponding chiral alcohol with 99.9% conversion and 98.8% ee. Considering that L3 derived from cinchonine had similar catalytic performance to L4 derived from quinidine, new ligand L10 similar to L5 with one methoxy group on benzene ring was synthesized and applied to the asymmetric hydrogenation of template substrate. 99.6% conversion and 97.6% ee was obtained. Hence, L5 was employed as better ligand in subsequent experiments.Open in a separate windowFig. 1The effect of different bases for the asymmetric hydrogenation of acetophenone (substrate/Ru/L5 = 500/1/2, ketones: 0.429 mol L−1, base: 0.15 mol L−1, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.).Open in a separate windowFig. 2The effect of different solvents for the asymmetric hydrogenation of acetophenone. (substrate/Ru/L5 = 1000/1/2, ketones: 0.858 mol L−1, Ba(OH)2: 0.15 mol L−1, solvent: 2 mL, 30 °C, 6 MPa, 2 h.).The effect of different ligand for the asymmetric hydrogenation of acetophenonea
EntryLigandsCon./%ee/%Config
1L147.578.2 R
2L256.177.8 R
3L3>9994.0 S
4L480.897.0 S
5L5>9998.8 S
6L654.298.0 S
7L72.184.2 S
8L891.198.0 S
9L936.592.8 S
10L10>9997.6 S
Open in a separate windowaSubstrate/Ru/L = 2000/1/2, ketones: 1.715 mol L−1, Ba(OH)2: 0.15 mol L−1, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.In order to evaluate the general applicability of this method, we have surveyed the substrate scope. As can be discerned from the data in Fig. 3, most of aryl alkyl ketones P1–P21 were hydrogenated with very high enantioselectivities (97.1–99.9% ee). Under the conditions employed, the electron effect and steric hindrance seemed to have no significant impact on the enantioselectivities of asymmetric hydrogenation. However, the activities were slightly affected by steric hindrance, especially ortho-substituted group. Significantly, Ru/L5 showed high enantioselectivity 98.2% in the hydrogenation of [3,5-bis(trifluoromethyl)phenyl]ethanone and its corresponding enantiopure alcohol P21 was key chiral intermediates for the NK-1 receptor antagonist aprepitant.57,58 Additionally, chiral heteroaromatic alcohols containing nitrogen, oxygen or sulfur in the heterocyclic ring were considerable organic synthetic intermediate in pharmaceuticals and organic synthesis.59–61 Nevertheless, due to the coordination ability of the heteroaromatic moiety, the asymmetric hydrogenation of heteroaromatic ketones has been less investigated. Surprisingly, the protocol was found to be very effective for asymmetric hydrogenation of various heteroaromatic ketones P22–P35. The substrates were all well reduced smoothly to afford the corresponding chiral alcohol with 97.1–99.9% ee. Notably, meta- and para-acetyl pyridines, generally as a challenging hydrogenation substrates62–64 owe to stronger coordination ability, were also hydrogenated with up to 97.2% ee (P33 and P34). Gratifyingly, 97.4 ee was obtained when acetonaphthone employed (P36). Benzo-fused seven-membered cyclic ketone proceeded well to afford the corresponding chiral alcohols with 99.6% ee (P37). To further explore substrate scope, we checked the effectiveness of method for asymmetric hydrogenation of unsaturated ketones. Although, both substrates were hydrogenated with high yield, only medium enantioselectivity 73.8 and 78.3% ee were given, respectively.Open in a separate windowFig. 3Asymmetric hydrogenation of ketones catalyzed by Ru/L5. (Substrate/Ru/L5 = 200/1/2, ketones: 0.171 mol L−1, Ba(OH)2: 0.15 mol L−1, MeOH: 2 mL, 30 °C, 6 MPa, 2 h, isolated yield, ee was determined by GC or HPLC on chiral stationary phase (see the ESI); asubstrate/Ru/L5 = 2000/1/2; bsubstrate/Ru/L5 = 100/1/2, 25 °C; csubstrate/Ru/L5 = 50/1/2, 25 °C, 24 h; dsubstrate/Ru/L5 = 25 °C; esubstrate/Ru/L5 = 50/1/2, 4 h; fEtOH).To understand the mechanism of the reaction, NMR was introduced to investigated active species. Single peak at δ = 19.91 ppm belonging to phenyl vinyl group of the complex disappeared in the 1H NMR spectrum when the complex was mixed with the ligand (Fig. S1, ESI). In the meantime, 31P NMR spectrum of the mixture exhibited new singlet at δ = 55.71 ppm (s) with the signal of complex disappearing (Fig. S2, ESI). These maybe indicated the formation of ruthenium complex A. Subsequently, a new weak signal was generated in the 31P NMR spectrum with the introduction of hydrogen and base (Fig. S3, ESI). These may indicate the formation of ruthenium hydride complexes. Meanwhile, the 1H NMR spectrum exhibited several weak signals below 0 ppm (Fig. S4, ESI). These data also verified the formation of ruthenium hydride complexes. Reference to relevant literature,65–67 the proposed catalytic cycle for the asymmetric hydrogenation of ketones with the ruthenium complex was shown in Scheme 1. First, the ruthenium complex reacted with ligands to form complex A. In the presence of base and hydrogen, the complex A lost two chlorine atoms to transform into dihydride complex B. Then, a hydridic Ru–H and a protic N–H unit were transferred from dihydride B to the carbonyl group of the ketones through the transition state TS to produce chiral alcohol. And the ruthenium complex lost two hydrogen atoms to form complex C. Finally, dihydride B was regenerated in hydrogen atmosphere. Compared with the reported iridium catalytic system with the same chiral ligands, the hydrogenation activity of the ruthenium catalytic system decreased significantly although maintained high enantioselectivity. The result indicates that the selection of metals was as important as chiral ligands for asymmetric hydrogenation.Open in a separate windowScheme 1Proposed mechanism for the asymmetric hydrogenation.  相似文献   
965.
目的:探讨利妥昔单抗(RTX)治疗儿童难治性激素耐药型肾病综合征(SRNS)的疗效和安全性。方法:回顾性分析2013年9月至2018年3月东部战区总医院儿科收治并接受RTX治疗的10例难治性SRNS患儿的临床资料。结果:10例患儿发病年龄(4.47±2.75)岁,男女各5例;5例(50%)肾活检为局灶节段性肾小球肾炎,...  相似文献   
966.
967.
正To the Editor : Liver transplantation (LT) has become a major and effective therapeutic approach for end-stage liver disease [1] . However, 10- year graft and patient survival rates remained low with 54% and 61%, respectively [2] . Improving the outcome of long-term LT has become a major focus of the transplantation community.  相似文献   
968.
5-Hydroxymethylfurfural (HMF) is a valuable platform chemical derived from biomass and lots of research focuses on the synthesis of HMF from fructose and glucose. Herein, conversion of bio-carbohydrates to 5-hydroxymethylfurfural (HMF) was studied in the three-component deep eutectic solvent (DES) system, which was composed of choline chloride (ChCl), boric acid and substrates such as fructose, glucose and sucrose. Bio-carbohydrates handled under typical reaction conditions gave satisfactory conversion (44% for fructose and 31% for glucose) and yield of HMF (35% for fructose and 21% for glucose) in 1 h. Moreover, owing to the benefits of DES, the initial substrate content could be higher and the reaction temperature could be reduced, thus side reactions were effectively avoided and the selectivity of HMF was better (ranging from 79% to 100% for fructose and from 65% to 100% for glucose). We believe this method could provide a promising alternative for conversion of bio-carbohydrates to HMF and a better utilization of biomass.

The conversion process of fructose and glucose in the three-component DES system. Substrates such as fructose, glucose and sucrose treated with this DES system could convert to HMF in a satisfactory yield and selectivity.  相似文献   
969.
We appreciate the question raised in a discussion with a reader and the editor about an instrument for outcome measure of the quality of life among people with ...  相似文献   
970.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号