全文获取类型
收费全文 | 6266篇 |
免费 | 394篇 |
国内免费 | 146篇 |
专业分类
耳鼻咽喉 | 23篇 |
儿科学 | 65篇 |
妇产科学 | 60篇 |
基础医学 | 1194篇 |
口腔科学 | 134篇 |
临床医学 | 425篇 |
内科学 | 1017篇 |
皮肤病学 | 105篇 |
神经病学 | 465篇 |
特种医学 | 99篇 |
外国民族医学 | 1篇 |
外科学 | 242篇 |
综合类 | 444篇 |
预防医学 | 312篇 |
眼科学 | 43篇 |
药学 | 1821篇 |
中国医学 | 144篇 |
肿瘤学 | 212篇 |
出版年
2023年 | 70篇 |
2022年 | 126篇 |
2021年 | 215篇 |
2020年 | 173篇 |
2019年 | 167篇 |
2018年 | 162篇 |
2017年 | 183篇 |
2016年 | 202篇 |
2015年 | 201篇 |
2014年 | 288篇 |
2013年 | 476篇 |
2012年 | 226篇 |
2011年 | 281篇 |
2010年 | 209篇 |
2009年 | 258篇 |
2008年 | 276篇 |
2007年 | 251篇 |
2006年 | 247篇 |
2005年 | 226篇 |
2004年 | 223篇 |
2003年 | 164篇 |
2002年 | 171篇 |
2001年 | 152篇 |
2000年 | 129篇 |
1999年 | 134篇 |
1998年 | 108篇 |
1997年 | 99篇 |
1996年 | 95篇 |
1995年 | 108篇 |
1994年 | 104篇 |
1993年 | 103篇 |
1992年 | 102篇 |
1991年 | 90篇 |
1990年 | 81篇 |
1989年 | 65篇 |
1988年 | 71篇 |
1987年 | 84篇 |
1986年 | 60篇 |
1985年 | 68篇 |
1984年 | 81篇 |
1983年 | 66篇 |
1982年 | 41篇 |
1981年 | 49篇 |
1980年 | 39篇 |
1979年 | 30篇 |
1978年 | 21篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1974年 | 8篇 |
1971年 | 2篇 |
排序方式: 共有6806条查询结果,搜索用时 46 毫秒
1.
Emeline Colomba Patricia Pautier Fanny Pommeret Alexandra Leary 《Expert review of anticancer therapy》2019,19(6):437-446
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
2.
摘要:抗生素的研发与使用有效杀灭和抑制了众多病原菌,挽救了无数人的生命,但由于抗生素的不合理使用,导致细菌耐
药不断出现,耐药菌的感染已严重地威胁人类的生命健康。为此,本文主要对近年来临床上常用的抗生素如β-内酰胺类、喹诺酮
类、氨基糖苷类药物以及新型抗菌药物如抗菌肽和纳米颗粒的应用研究进行总结分析与探讨,为临床上治疗疾病提供一些参考。 相似文献
3.
O. Morris M. Fairclough J. Grigg C. Prenant A. McMahon 《Journal of labelled compounds & radiopharmaceuticals》2019,62(1):4-23
Affinity peptide and protein‐ (APP) based radiotracers are an increasingly popular class of radiotracer in positron emission tomography (PET), which was once dominated by the use of small molecule radiotracers. Radiolabelled monoclonal antibodies (mAbs) are important examples of APPs, yet a preference for smaller APPs, which exhibit fast pharmacokinetics and permit rapid PET aided diagnosis, has become apparent. 18F exhibits favourable physical characteristics for APP radiolabelling and has been described as an ideal PET radionuclide. Notwithstanding, 18F radiolabelling of APP is challenging, and this is echoed in the literature where a number of diverse approaches have been adopted. This review seeks to assess and compare the approaches taken to 18F APP radiolabelling with the intention of highlighting trends within this expanding field. Generic themes have emerged in the literature, namely the use of mild radiolabelling conditions, a preference of site‐specific methodologies with an impetus for short, automated procedures which produce high‐yielding [18F]APPs. 相似文献
4.
双环[1.1.1]戊烷(BCP)是一种具有三维立体结构的桥环骨架,其作为苯环、叔丁基和炔烃的生物电子等排体,已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大,BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结,旨在为新药研发人员提供参考。 相似文献
5.
BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described. 相似文献
6.
GIUSEPPE PERSEO MAURO GIGLI ROBERTO DE CASTIGLIONE 《Chemical biology & drug design》1987,29(4):478-485
The synthesis of TPH-13 (Glp-Glu-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met-OH), a tridecapeptide isolated from the skin of the South American frog Phyllomedusa rohdei, is described and alternative approaches are discussed. 相似文献
7.
GAETANO BARBATO GABRIELLA D'AURIA LIVIO PAOLILLO GIANCARLO ZANOTTI 《Chemical biology & drug design》1991,37(5):388-398
Bycyclic peptides are useful model molecules that can mimic the constrained local folding of a great number of natural peptides and proteins, such as ionophoric peptides, enzyme active site, and ligand-receptor active site. The synthesis of the bicyclic title compound with the liquid phase method is described with experimental details. Of particular interest is the heterodetic closure of the second ring. The peptide showed a complexing activity with metal cations like Ba2+, Ca2+, and Mg2+ . The free bicyclic peptide conformation in solution has been studied by means of NMR spectroscopy and a plausible structure model worked out with model building on NMR constraints is proposed. 相似文献
8.
M. D. Taylor M. L. de Ceballos S. Rose P. N. Chong P. Jenner C. D. Marsden 《Journal of neural transmission (Vienna, Austria : 1996)》1991,3(2):99-108
Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met5]-enkephalin, [Leu5]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met5]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu5]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met5]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease. 相似文献
9.
10.
MONIQUE DAVRIL MIREILLE GUAY KIA-KI HAN FRANCOIS LAMY 《Chemical biology & drug design》1987,29(1):68-77
This report describes the use of photolysis and ozonolysis as a means of achieving complete cleavage of the pyridinium ring of (iso)desmosine in crosslinked elastin peptides. Although photolysis leads to the opening of the ring with concomitant formation of lysine, the peptide chains remain attached. Subsequent ozonolysis is able to completely achieve the cleavage of the rest of the ring skeleton, thus leading to the separation of the peptide chains. Formation of new amino acids, i.e. α-aminoadipic and glutamic acids, is emphasized. Localization of these amino acids within the released peptides should be of help in structural investigations on the crosslinking zones involving either isodesmosine or desmosine. However, other amino acids such as tyrosine and phenylalanine are sensitive to this procedure and side reactions occur which are responsible for peptide bond cleavage with the formation of breakdown products. 相似文献