全文获取类型
收费全文 | 7764篇 |
免费 | 520篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 168篇 |
儿科学 | 290篇 |
妇产科学 | 203篇 |
基础医学 | 1047篇 |
口腔科学 | 376篇 |
临床医学 | 513篇 |
内科学 | 1763篇 |
皮肤病学 | 180篇 |
神经病学 | 572篇 |
特种医学 | 223篇 |
外科学 | 1048篇 |
综合类 | 42篇 |
预防医学 | 801篇 |
眼科学 | 100篇 |
药学 | 457篇 |
中国医学 | 45篇 |
肿瘤学 | 469篇 |
出版年
2023年 | 70篇 |
2022年 | 122篇 |
2021年 | 253篇 |
2020年 | 142篇 |
2019年 | 222篇 |
2018年 | 299篇 |
2017年 | 208篇 |
2016年 | 191篇 |
2015年 | 213篇 |
2014年 | 288篇 |
2013年 | 355篇 |
2012年 | 497篇 |
2011年 | 533篇 |
2010年 | 354篇 |
2009年 | 261篇 |
2008年 | 430篇 |
2007年 | 423篇 |
2006年 | 391篇 |
2005年 | 394篇 |
2004年 | 361篇 |
2003年 | 306篇 |
2002年 | 271篇 |
2001年 | 186篇 |
2000年 | 224篇 |
1999年 | 188篇 |
1998年 | 67篇 |
1997年 | 44篇 |
1996年 | 37篇 |
1995年 | 42篇 |
1994年 | 43篇 |
1993年 | 39篇 |
1992年 | 91篇 |
1991年 | 62篇 |
1990年 | 71篇 |
1989年 | 72篇 |
1988年 | 57篇 |
1987年 | 55篇 |
1986年 | 42篇 |
1985年 | 42篇 |
1984年 | 32篇 |
1983年 | 25篇 |
1979年 | 22篇 |
1978年 | 17篇 |
1976年 | 21篇 |
1975年 | 21篇 |
1974年 | 23篇 |
1973年 | 23篇 |
1971年 | 21篇 |
1970年 | 19篇 |
1969年 | 16篇 |
排序方式: 共有8297条查询结果,搜索用时 15 毫秒
1.
N. S. Hari Narayana Moorthy Sergio F. Sousa Maria J. Ramos Pedro A. Fernandes 《Medicinal chemistry research》2016,25(7):1340-1357
Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets. 相似文献
2.
3.
M. L. Hernández J. J. Fernández-Ruiz R. de Miguel J. A. Ramos 《Journal of neural transmission (Vienna, Austria : 1996)》1991,83(1-2):77-84
Summary In this work, we have studied the time-course of the effects of pharmacological administration of ovarian steroids on tyrosine hydroxylase (TH) activity in the limbic forebrain of ovariectomized rats. Administration of estradiol produced a late decrease in TH activity. This effect was found 24 hours after the last steroid injection, disappearing at 32 hours. It was antagonized by progesterone, since a single injection of this steroid to estradiol-pretreated rats reversed to control values the estradiol-induced decrease. Nevertheless, the administration of progesterone after estradiol treatment caused a short-time decrease in the limbic activity of TH, which was observed 4 hours after the last steroid injection, disappearing subsequently. On the other hand, the administration of progesterone alone produced a biphasic effect, with a reduction at 24 hours, followed by an increase at 32 hours. These effects were only observed in the animals non-treated with estradiol, disappearing with a previous treatment with estrogens. Hence, it can be concluded that both ovarian steroids may affect the limbic TH activity. Thus, estradiol produced a late inhibitory effect on the activity of this enzyme, which was antagonized by progesterone. Administration of the last one to estradiol-treated rats produced a short-time inhibitory effect, whereas its administration to non-treated rats produced a late biphasic effect (inhibition followed by stimulation), which was not observed in estradiol-treated rats. 相似文献
4.
The health care supervisor responsible for establishing a therapeutic milieu within a traditional hospital organization will have greater success if these suggested management strategies are employed. Decentralizing, improving organizational communication, and clarifying interdisciplinary role relationships are the strategies that support the integration of differing organizational approaches to management. 相似文献
5.
6.
Ignacio Alvarez Alvarez M.D. Pedro Sanchez Lazo Ph.D. Sofia Ramos Gonzalez Ph.D. J. Pablo Rodrigo Tapia M.D. Faustino Nunez Batalla M.D. Carlos Suarez Nieto M.D. 《American journal of otolaryngology》1997,18(6):375
Purpose: Increasingly, evidence has shown that human papillomavirus (HPV) plays a role in the induction of certain carcinomas. The presence of HPV sequences in 56 previously untreated oral and pharyngolaryngeal carcinomas was examined by the polymerase chain reaction (PCR).Materials and Methods: After DNA extraction, samples underwent 40 replication cycles with specific oligonucleotide primers corresponding to sequences from the E6 open-reading frame of HPV-6b, HPV-16, and HPV-18. To determine the E6 genomic integration, positive samples were processed with specific primers for the corresponding HPV L1 genes. Genomic HPV DNA cloned into PBR 322 was used as positive control.Results: HPV E6 DNA of the 6b and 16 types was detected in 14 patients (25%). The L1 gene was not present.Conclusion: Detected HPV E6 DNA might be integrated into the cell genome in the positive cases as indicated by the absence of the L1 gene-coding for the viral capside. Histological and clinical parameters, such as tumor location, degree of differentiation, stage, recurrence, and survival rates, were unrelated to the presence of HPV. 相似文献
7.
8.
Hydrocephalus and cavernoma of the cauda equina 总被引:1,自引:0,他引:1
The association of a tumor of the cauda equina and hydrocephalus is unusual. We report a case of hydrocephalus with normal pressure associated with an equally rare affliction, a cavernous angioma of the cauda equina, which regressed after surgical ablation. The physiological mechanism involved is discussed. 相似文献
9.
F. M. González Valverde F. Mauri Barberá M. Molto Aguado N. Torregrosa A. Hernández Quiles F. Menárguez Pina M. J. Gómez Ramos M. García Real J. A. Barreras Mateos J. L. Vázquez Rojas 《European Surgery》2004,36(4):253-256
Summary BACKGROUND: Endometriosis is a relatively common pathology in women of childbearing age and of low parity but rarely shows
extraperitoneal involvement. The main aim of this paper is to raise the attention of specialists to the necessity of carrying
out penetrating diagnosis of nonspecific extraperitoneal masses occurring in women of reproductive age. METHODS: We performed
a retrospective review of six patients diagnosed with extraperitoneal endometriosis who were treated at the Vega Baja University
Hospital (Spain) during the last 5 years. RESULTS: Surgical treatment had positive results in five patients. The preoperative
diagnosis was correctly made in only two patients. The accurate aetiology of endometriosis remains unknown and diagnosis is
based on clinical and cytopathological findings. CONCLUSIONS: Surgical treatment of extraperitoneal endometriosis is recommended.
However, postoperative follow-up is obligatory and hormonal suppressive therapy may be necessary. Medical treatment with gestagens,
Danazol, or agonists of the gonadotropin-releasing hormone are ineffective in endometriomas which are bigger than 2 cm.
相似文献
10.
Jorge Polónia Jo?o Maldonado Rui Ramos Susana Bertoquini Mary Duro Cristina Almeida Jo?o Ferreira Loide Barbosa José Alberto Silva Luís Martins 《Revista portuguesa de cardiologia》2006,25(9):801-817
BACKGROUND: Portugal has one of the highest mortality rates from stroke, a high prevalence of hypertension and probably a high salt intake level. AIM: To evaluate Portuguese salt intake levels and their relationship to blood pressure and arterial stiffness in a sample of four different adult populations living in northern Portugal. METHODS: A cross-sectional study evaluating 24-hour urinary excretion of sodium (24 h UNa+), potassium and creatinine, blood pressure (BP), and pulse wave velocity (PWV) as an index of aortic stiffness in adult populations of sustained hypertensives (HT), relatives of patients with previous stroke (Fam), university students (US) and factory workers (FW), in the context of their usual dietary habits. RESULTS: We evaluated a total of 426 subjects, mean age 50 +/- 22 years, 56% female, BMI 27.9+/-5.1, BP 159/92 mmHg, PWV 10.4+/-2.2 m/s, who showed mean 24h UNa+ of 202 +/- 64 mmol/d, corresponding to a daily salt intake of 12.3 g (ranging from 5.2 to 24.8). The four groups were: HT: n = 245, 49 +/- 18 years, 92% of those selected, 69% treated, BP 163/94 mmHg, PWV 11.9 m/s, 24 h UNa+ 212 mmol/d, i.e. 12.4 g/d of salt); Fam: n = 38, 64 +/- 20 years, 57 % of those selected, BP 144/88 mmHg, PWV 10.5 m/s, 24 h UNa+ 194 mmol/d, i.e. 11.1 g/d of salt; US: n = 82, 22 +/- 3 years, 57% of those selected, BP 124/77 mmHg, PWV 8.7 m/s, 24h UNa+ 199 mmol/d, i.e. 11.3 g/d of salt; FW: n = 61, 39 9 years, 47% of those selected, BP 129/79 mmHg, PWV 9.5 m/s, 24 h UNa+ 221 mmol/d, i.e. 12.9 g/d of salt. The ratio of urinary sodium/potassium excretion (1.9 (0.4) was significantly higher in HT than the other three groups. In the 426 subjects, 24h UNa+ correlated significantly (p < 0.01) with systolic BP (r = 0.209) and with PWV (r=0.256) after adjustment for age and BP. Multivariate analysis showed that BP, age and 24h UNa+ correlated independently with PWV taken as a dependent variable. CONCLUSIONS: Four different Portuguese populations showed similarly high mean daily salt intake levels, almost double those recommended by the WHO. Overall, high urinary sodium excretion correlated consistently with high BP levels and appeared to be an independent determining factor of arterial stiffness. These findings suggest that Portugal in general has a high salt intake diet, and urgent measures are required to restrict salt consumption in order to prevent and treat hypertensive disease and to reduce overall cardiovascular risk and events. 相似文献