全文获取类型
收费全文 | 39328篇 |
免费 | 4356篇 |
国内免费 | 3021篇 |
专业分类
耳鼻咽喉 | 432篇 |
儿科学 | 358篇 |
妇产科学 | 310篇 |
基础医学 | 3796篇 |
口腔科学 | 635篇 |
临床医学 | 4967篇 |
内科学 | 5083篇 |
皮肤病学 | 469篇 |
神经病学 | 1734篇 |
特种医学 | 1686篇 |
外国民族医学 | 11篇 |
外科学 | 4826篇 |
综合类 | 8270篇 |
现状与发展 | 16篇 |
一般理论 | 2篇 |
预防医学 | 3077篇 |
眼科学 | 903篇 |
药学 | 4408篇 |
38篇 | |
中国医学 | 2761篇 |
肿瘤学 | 2923篇 |
出版年
2024年 | 209篇 |
2023年 | 869篇 |
2022年 | 2067篇 |
2021年 | 2502篇 |
2020年 | 1979篇 |
2019年 | 1478篇 |
2018年 | 1487篇 |
2017年 | 1483篇 |
2016年 | 1301篇 |
2015年 | 2020篇 |
2014年 | 2375篇 |
2013年 | 2447篇 |
2012年 | 3271篇 |
2011年 | 3549篇 |
2010年 | 2569篇 |
2009年 | 2097篇 |
2008年 | 2294篇 |
2007年 | 2263篇 |
2006年 | 1990篇 |
2005年 | 1844篇 |
2004年 | 1200篇 |
2003年 | 996篇 |
2002年 | 838篇 |
2001年 | 647篇 |
2000年 | 584篇 |
1999年 | 567篇 |
1998年 | 288篇 |
1997年 | 277篇 |
1996年 | 228篇 |
1995年 | 197篇 |
1994年 | 160篇 |
1993年 | 82篇 |
1992年 | 91篇 |
1991年 | 89篇 |
1990年 | 82篇 |
1989年 | 62篇 |
1988年 | 54篇 |
1987年 | 36篇 |
1986年 | 28篇 |
1985年 | 11篇 |
1984年 | 17篇 |
1982年 | 11篇 |
1981年 | 10篇 |
1979年 | 6篇 |
1978年 | 11篇 |
1977年 | 5篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1972年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
82.
Nicole-Ann Lim Ooiean Teng Chester Yan Hao Ng Lena X. Y. Bao Paul Anantharajah Tambyah Amy M. L. Quek Raymond C. S. Seet 《Annals of medicine》2022,54(1):1488
BackgroundAccumulating data suggest antiviral effects of povidone-iodine against the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This narrative review aims to examine the antiviral mechanisms of povidone-iodine, efficacy of povidone-iodine against the SARS-CoV-2 virus, and safety of povidone-iodine to human epithelial cells and thyroid function.MethodsWe searched the electronic databases PubMed, Embase, Cochrane Library, ClinicalTrials.gov and World Health Organization’s International Clinical Trials Registry Platform for articles containing the keywords “povidone-iodine”, “SARS-CoV-2” and “COVID-19” from database inception till 3 June 2021.ResultsDespite in vitro data supporting the anti-SARS-CoV-2 effects of povidone-iodine, findings from clinical studies revealed differences in treatment response depending on study settings (healthy vs. hospitalized individuals), treatment target (nasal vs. oral vs. pharynx), method of administration (oral rinse vs. gargle vs. throat spray) and choice of samples used to measure study endpoints (nasopharyngeal vs. saliva). One large-scale clinical trial demonstrated reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak. Povidone-iodine is also used to disinfect the oro-pharyngeal space prior to dental or otolaryngology procedures. Although existing data suggest minimal impact of povidone-iodine on thyroid function, high-quality safety data are presently lacking.ConclusionsPovidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.
Key messages
- Accumulating data suggest antiviral effects of povidone-iodine against the SARS-CoV-2 virus.
- Findings from clinical studies reveal differences in treatment response depending on study settings, treatment target, method of administration and choice of samples used to measure study endpoints. One large-scale clinical trial observed reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak.
- Povidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.
83.
Qiumin Huang Lixin Hao Liusen Wang Hongru Jiang Weiyi Li Shaoshunzi Wang Xiaofang Jia Feifei Huang Huijun Wang Bing Zhang Gangqiang Ding Zhihong Wang 《Nutrients》2022,14(10)
There is a lack of studies on the association between whole grain intake and cardiometabolic risk factors in China and the current definition of whole grains is inconsistent. This study defined whole grains in two ways, Western versus traditional, and examined their associations with the risks of major cardiometabolic factors (CMFs) among 4706 Chinese adults aged ≥18 years, who participated in surveys both in 2011 and in 2015. Diet data were collected by consecutive 3 d 24 h recalls, together with household seasoning weighing. Whole grains were defined as grains with a ratio of fiber to carbohydrate of ≥0.1, while coarse grains were defined as grains except for rice and its products, and wheat and its products. Multivariable logistic regressions were modeled to analyze the associations of intakes of whole grains and coarse grains, respectively, with risks of major CMFs including obesity-, blood pressure-, blood glucose- and lipid-related factors, which were defined by International Diabetes Federation and AHA/NHLBI criteria. After adjusting for potential confounders, the odds of elevated LDL-C decreased with the increasing intake levels of whole grains (OR 0.64, 95% CI 0.46–0.88, p-trend < 0.05). Moreover, adults with the whole grain intake of 50.00 to 150.00 g/day had 27% lower odds of overweight and obesity (OR 0.73, 95% CI 0.54–0.99) and 31% lower odds of elevated LDL-C (OR 0.69, 95% CI 0.49–0.96), as compared with non-consumers. In conclusion, given the significant nutrient profiles of whole grains and coarse grains, the adults with higher intakes of whole grains only may have a lower risk of LDL-C and overweight and obesity. 相似文献
84.
Xiaoran Chang Qian Lin Qun Zhang Junying Hu Gulbahar Tursun Yingrui Deng Chunguang Guo Xinping Wang 《Viruses》2022,14(5)
Here, we report the characterization of 13 novel caprine/ovine enterovirus strains isolated from different regions in China during 2016–2021. Immunoperoxidase monolayer assay showed that these viral strains shared strong cross-reaction with the previously reported caprine enterovirus CEV-JL14. Alignment analysis of the complete nucleotide sequences revealed 79.2%–87.8% and 75.0%–76.7% sequence identity of these novel caprine enterovirus strains to CEV-JL14 and TB4-OEV, respectively. Phylogenetic analyses clustered these novel strains to EV-G based on the amino acid sequences of P1 and 2C+3CD. Moreover, phylogenetic analysis of these caprine enterovirus strains identified three new EV-G types using VP1 sequences. These results demonstrate the genetic variations and the evolution of caprine enterovirus. 相似文献
85.
Ling Zhang Qian Chen Linlin Li Jian Jiang Hao Sun Li Li Ting Liu Lin Zhang Chun Li 《RSC advances》2022,12(23):14912
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
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
Entry | Ligands | Con./% | ee/% | Config |
---|---|---|---|---|
1 | L1 | 47.5 | 78.2 | R |
2 | L2 | 56.1 | 77.8 | R |
3 | L3 | >99 | 94.0 | S |
4 | L4 | 80.8 | 97.0 | S |
5 | L5 | >99 | 98.8 | S |
6 | L6 | 54.2 | 98.0 | S |
7 | L7 | 2.1 | 84.2 | S |
8 | L8 | 91.1 | 98.0 | S |
9 | L9 | 36.5 | 92.8 | S |
10 | L10 | >99 | 97.6 | S |
86.
Granular materials are widespread in nature and human production, and their macro-mechanical behavior is significantly affected by granule movement. The development of computer vision has brought some new ideas for measuring the numerical information (including the amount of translation, the rotation angle, velocity, acceleration, etc.) of dynamic granular materials. In this paper, we propose a numerical measurement method for dynamic granular materials based on computer vision. Firstly, an improved video instance segmentation (VIS) network is introduced to perform end-to-end multi-task learning, and its temporal feature fusion module and tracking head with long-sequence external memory can improve the problems of poor video data quality and high similarity in appearance of granular materials, respectively. Secondly, the numerical information can be extracted through a series of post-processing steps. Finally, the effectiveness of the measurement method is verified by comparing the numerical measurement results with the real values. The experimental results indicate that our improved VIS obtains an average precision (AP) of 76.6, the relative errors and standard deviations are maintained at a low level, and this method can effectively be used to measure the numerical information of dynamic granular materials. This study provides an intelligent proposal for the task of measuring numerical information of dynamic granular materials, which is of great significance for studying the spatial distribution, motion mode and macro-mechanical behavior of granular materials. 相似文献
87.
Lihua Xu Huiru Cui Yanyan Wei Zhenying Qian Xiaochen Tang Yegang Hu Yingchan Wang Hao Hu Qian Guo Yingying Tang Tianhong Zhang Jijun Wang 《上海精神医学》2022,35(3)
BackgroundSelf-reflectiveness, one dimension of cognitive insight, plays a protective role in an individual’s mental state. Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.AimsThis study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.MethodsA total of 181 subjects, including individuals with attenuated positive symptoms (APS, n=122) and patients with first-episode psychosis (FEP, n=59), completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale. All subjects were classified into three groups according to their level of self-reflectiveness: low level (LSR, n=59), medium level (MSR, n=67) and high level (HSR, n=55). Both linear and non-linear relationships between self-reflectiveness and clinical symptoms were explored.ResultsMore individuals with APS were classified into the MSR group, while more patients with FEP were classified into the LSR group. The LSR group demonstrated less awareness of illness than the MSR and HSR groups, more stereotyped thinking and poorer impulse control but less anxiety than the MSR group, and lower levels of blunted affect and guilt feelings than the HSR group. The MSR group demonstrated lower stereotyped thinking than the HSR group. Compared to the LSR group, the MSR group had increased self-reflectiveness, improved awareness of illness, decreased stereotyped thinking, and better impulse control, but increased feelings of guilt. The HSR group showed increased stereotyped thinking when compared to the MSR group, but the other variables did not change significantly between these two groups. Overall, self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness, a U-shaped relationship with stereotyped thinking and poor impulse control, and an almost linear relationship with anxiety and guilt feelings.ConclusionsSelf-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level. 相似文献
88.
多指标正交试验优选白术芍药散提取工艺 总被引:3,自引:1,他引:3
白术芍药散是中医传统名方,临床对于腹泻有确切的治疗效果.然而,目前有关白术芍药散的提取工艺报道较少.该试验利用正交试验的方法,以复方中10个指标性成分和浸出物的含量作为指标,采用综合加权评分法处理数据,对提取工艺中乙醇浓度、溶剂倍量、浸泡时间、提取时间4个因素进行考察,以优化白术芍药散提取工艺.结果得出白术芍药散的最佳提取工艺为加入12倍量70%乙醇,浸泡1h,提取2次,每次2h.其中提取时间有显著影响.优化后的提取工艺稳定可靠,可为进一步开发利用该处方提供参考. 相似文献
89.
目的:建立同时测定人血浆中雷米普利和雷米普利拉浓度的液相色谱-质谱方法。方法:以喹那普利为内标,血浆样品经固相萃取小柱提取后,采用HPLC-MS(TOF)联用技术,以电喷雾(ESI)作为接口技术,以宽的m/z为数据采集范围检测后,选择准分子离子[M H] 作为检测离子,进行滤过、积分的方式检测,同时测定人血浆中雷米普利和雷米普利拉的浓度。结果:雷米普利和雷米普利拉的线性范围分别为1~80μg·L-1和0.5~40μg·L-1,日内精密度与日间RSD均小于10%。结论:该测定方法具有灵敏、专一和快速的优点,可满足雷米普利在人体内药动学研究的要求。 相似文献
90.