全文获取类型
收费全文 | 2796篇 |
免费 | 227篇 |
国内免费 | 53篇 |
专业分类
耳鼻咽喉 | 48篇 |
儿科学 | 169篇 |
妇产科学 | 96篇 |
基础医学 | 197篇 |
口腔科学 | 88篇 |
临床医学 | 216篇 |
内科学 | 718篇 |
皮肤病学 | 72篇 |
神经病学 | 75篇 |
特种医学 | 229篇 |
外国民族医学 | 1篇 |
外科学 | 346篇 |
综合类 | 141篇 |
预防医学 | 159篇 |
眼科学 | 68篇 |
药学 | 274篇 |
中国医学 | 12篇 |
肿瘤学 | 167篇 |
出版年
2023年 | 25篇 |
2022年 | 74篇 |
2021年 | 108篇 |
2020年 | 61篇 |
2019年 | 86篇 |
2018年 | 97篇 |
2017年 | 103篇 |
2016年 | 83篇 |
2015年 | 80篇 |
2014年 | 122篇 |
2013年 | 151篇 |
2012年 | 157篇 |
2011年 | 144篇 |
2010年 | 123篇 |
2009年 | 134篇 |
2008年 | 96篇 |
2007年 | 138篇 |
2006年 | 84篇 |
2005年 | 65篇 |
2004年 | 47篇 |
2003年 | 38篇 |
2002年 | 30篇 |
2001年 | 61篇 |
2000年 | 32篇 |
1999年 | 36篇 |
1998年 | 92篇 |
1997年 | 73篇 |
1996年 | 79篇 |
1995年 | 63篇 |
1994年 | 52篇 |
1993年 | 46篇 |
1992年 | 21篇 |
1991年 | 24篇 |
1990年 | 26篇 |
1989年 | 38篇 |
1988年 | 50篇 |
1987年 | 38篇 |
1986年 | 34篇 |
1985年 | 27篇 |
1984年 | 19篇 |
1983年 | 19篇 |
1982年 | 14篇 |
1980年 | 12篇 |
1979年 | 18篇 |
1978年 | 16篇 |
1977年 | 16篇 |
1976年 | 29篇 |
1975年 | 17篇 |
1974年 | 11篇 |
1966年 | 10篇 |
排序方式: 共有3076条查询结果,搜索用时 15 毫秒
101.
Farideh Badichi Akher Abdolkarim Farrokhzadeh Mahmoud E. S. Soliman 《Chemical biology & drug design》2019,93(5):798-810
11h is a very potent inhibitor against epidermal growth factor receptor triple mutation L858R/T790M/C797S (EGFRTM) with 13‐fold stronger potency than the FDA‐approved osimertinib. Recently, two new EGFRTM inhibitors, 11d and 11e , were reported which revealed 2.8‐ and 2.3‐fold stronger potency than 11h , respectively. 11h , 11d, and 11e have the same structures but differ only in their aliphatic chain length. However, the exact effects of differential aliphatic chain length on the inhibitory potencies of these compounds require further elaboration at the atomistic level, hence the objective of this report. Various computational tools were employed for this purpose. From our findings, it was revealed that van der Waals (vdW) interactions modulate the binding mechanisms of these inhibitors and play the most important role in the differential inhibitory activities of 11d , 11h, and 11e . The strong hydrogen bond formation between the aliphatic chain of 11d and key residue ARG841 was recognized as the reason for its higher activity and inhibitory potency relative to 11h and 11e . Moreover, the extension of the N‐terminal loop into the active site for vdW interaction with the phenyl group of 11e and carbon–hydrogen bond formed between the aliphatic chain of 11e and LEU718 engendered a higher activity of 11e than 11h . 相似文献
102.
Elliasu Y. Salifu Clement Agoni Fisayo A. Olotu Yussif M. Dokurugu Mahmoud E. S. Soliman 《Chemical biology & drug design》2019,94(5):1905-1918
The experimental inhibitory potency of benzamidine (BEN) paved way for further design and development of inhibitors that target β‐FXIIa. Structural dynamics of the loops and catalytic residues that encompass the binding pocket of β‐FXIIa and all serine proteases are crucial to their overall activity. Employing molecular dynamics and post‐MD analysis, this study sorts to unravel the structural and molecular events that accompany the inhibitory activity of BEN on human β‐FXIIa upon selective non‐covalent binding. Analysis of conformational dynamics of crucial loops revealed prominent alterations of the original conformational posture of FXIIa, evidenced by increased flexibility, decreased compactness, and an increased exposure to solvent upon binding of BEN, which could have in turn interfered with the essential roles of these loops in enhancing their procoagulation interactions with biological substrates and cofactors, altogether resulting in the consequential inactivation of FXIIa. A sustained interaction of the catalytic triad residues and key residues of the autolysis loop impeded their roles in catalysis which equally enhanced the inhibitory potency of BEN toward β‐FXIIa evidenced by a favorable binding. Findings provide essential structural and molecular insights that could facilitate the structure‐based design of novel antithrombotic compounds with enhanced inhibitory activities and low therapeutic risk. 相似文献
103.
This investigation examines the role of carboxyl functionalized multi-walled carbon nanotubes (COOH-MWCNTs) in the on- and off-axis flexure and the shear responses of thin carbon woven fabric composite plates. The chemically functionalized COOH-MWCNTs were used to fabricate epoxy nanocomposites and, subsequently, carbon woven fabric plates to be tested on flexure and shear. In addition to the neat epoxy, three loadings of COOH-MWCNTs were examined: 0.5 wt%, 1.0 wt% and 1.5 wt% of epoxy. While no significant statistical difference in the flexure response of the on-axis specimens was observed, significant increases in the flexure strength, modulus and toughness of the off-axis specimens were observed. The average increase in flexure strength and flexure modulus with the addition of 1.5 wt% COOH-MWCNTs improved by 28% and 19%, respectively. Finite element modeling is used to demonstrate fiber domination in on-axis flexure behavior and matrix domination in off-axis flexure behavior. Furthermore, the 1.5 wt% COOH-MWCNTs increased the toughness of carbon woven composites tested on shear by 33%. Microstructural investigation using Fourier Transform Infrared Spectroscopy (FTIR) proves the existence of chemical bonds between the COOH-MWCNTs and the epoxy matrix. 相似文献
104.
105.
106.
Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR‐PI376, as highly potent agonists at the human histamine H4 receptor (hH4R). While imidazole‐containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six‐membered heterocycles (piperidine, morpholine, thiomorpholine, and N‐methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C3–C5) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand‐binding assays exhibited only very weak activity at the hH1R and hH3R, while nearly all compounds were inactive at the hH2R and hH4R. In the case of piperidine‐containing compounds, moderate affinities at the hH3R over the single‐digit micromolar range were detected. 相似文献
107.
Gamliel-Lazarovich A Abassi Z Khatib S Tavori H Vaya J Aviram M Keidar S 《Atherosclerosis》2012,222(1):92-98
AimSerum paraoxonase 1 (PON1) is an HDL-associated lipolactonase and its association with hypertension is controversial. We studied the possible role of PON1 in blood pressure (BP) regulation, by using PON1 knockout (PON1KO) mice.Methods and resultsBoth, systolic and diastolic BPs were lower in PON1KO compared to WT mice. Hypotension detected in PON1KO is probably neither related to nitric oxide/guanylate cyclase-mediated vasodilation nor to angiotensin II or aldosterone-mediated vasoconstriction. Surprisingly, when challenged by high-salt diet, BP was further reduced in PON1KO mice. The later, pointed to a possible involvement of transient receptor potential vanilloid 4 (TRPV4), and indeed, administration of ruthenium red, a TRPV4 blocker, resulted in a sharp rise in BP. The protein levels of TRPV4 in kidneys of PON1KO were not higher than in WT. However, the renal level of 5,6-epoxyeicosatrienoic acid (5,6-EET), a TRPV4 specific agonist, was significantly higher in PON1KO compared with WT mice. 5,6-EET levels were further elevated under high-salt diet or administration of arachidonic acid. Injection of inhibitor of CYP450 epoxygenase resulted in increased BP in PON1KO mice. Injection of recombinant human PON1 resulted in elevation of BP and a concomitant reduction in renal content of 5,6-EET. PON1, in vitro, metabolized 5,6-EET, but not other EETs, to its corresponding diol. Vasodilation, blocked by excess of dietary K+ but not reversed by depletion of cellular Ca2+ stores, point to endothelial-derived hyperpolarization-like response.ConclusionThe present study shows causal, direct relationship between PON1 and blood pressure which is mediated, at least in part, by the regulation of 5,6-EET. 相似文献
108.
Heart disease and stroke statistics--2012 update: a report from the American Heart Association 总被引:1,自引:0,他引:1
Roger VL Go AS Lloyd-Jones DM Benjamin EJ Berry JD Borden WB Bravata DM Dai S Ford ES Fox CS Fullerton HJ Gillespie C Hailpern SM Heit JA Howard VJ Kissela BM Kittner SJ Lackland DT Lichtman JH Lisabeth LD Makuc DM Marcus GM Marelli A Matchar DB Moy CS Mozaffarian D Mussolino ME Nichol G Paynter NP Soliman EZ Sorlie PD Sotoodehnia N Turan TN Virani SS Wong ND Woo D Turner MB;American Heart Association Statistics Committee Stroke Statistics Subcommittee 《Circulation》2012,125(1):e2-e220
109.
To assess the possible association between the protein tyrosine phosphatases non-receptor 22 (PTPN22) gene 1858 CT polymorphism and the predisposition to systemic lupus erythematosus (SLE) in Egyptian patients and its influence on clinical and laboratory parameters. PTPN22 gene 1858 CT polymorphisms were analyzed in forty SLE patients and 20 normal controls by real-time polymerase chain reaction (PCR) technology, using the TaqMan 5-allele discrimination assay. Detailed history, clinical examination, and investigations were done to detect various organ involvement. The homozygous genotype TT was absent in both SLE and controls. The CC genotype was observed in 47.5% SLE and 80% controls; the CT genotype was found in 52.5% patients and 20% controls. The frequencies of the C and T alleles were 74 and 26% in SLE and 90 and 10% in controls, respectively. The presence of CT genotype increased the risk for developing SLE by 4.42. Renal involvement was significantly higher in SLE patients with CT (76.2%) compared to those with CC genotype (42.1%). 相似文献
110.
Soliman E Labib W el-Tantawi G Hamimy A Alhadidy A Aldawoudy A 《Rheumatology international》2012,32(6):1711-1720
The objective of this study is to evaluate the role of MMP-3 and MRI in assessing disease activity in sacroiliac joints of AS patients in comparison to the conventional measures Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum MMP-3 was measured in 30 patients who fulfilled the modified New York criteria for AS and in ten healthy volunteers. AS patients were categorized into those having high or low MMP-3 according to a cut-off value?=?7.1?ng/ml. MRI of the sacroiliac joints (SIJs) was performed on all patients. SIJs were evaluated for enhancement and subchondral bone marrow edema. Results of MMP-3 and findings on MRI were correlated with multiple clinical parameters including BASDAI, ESR and CRP. Serum MMP-3 was significantly elevated in AS patients with active disease. Elevated MMP-3 levels were significantly associated with high BASDAI (P?=?0.046), but not with ESR or CRP. MRI showed bone marrow edema and enhancement of SIJs in 19/30 patients with one patient showing enhancement only. These MRI findings were not correlated with MMP-3, BASDAI, CRP or ESR. In conclusion, serum MMP-3 is an objective measure reflecting clinical disease activity in AS. Bone marrow edema and enhancement detected by MRI of SIJs is another objective measure of disease activity, but are not correlated with MMP-3 or the conventional parameters as BASDAI, ESR, or CRP. Although both MMP-3 and MRI can reflect disease activity in AS they seem to be unrelated, perhaps each is reflecting a different aspect of disease activity. MMP-3 and MRI should be considered together with BASDAI in assessing disease activity and in guiding the available recommendations for initiation of biologics in AS. 相似文献