全文获取类型
收费全文 | 10207篇 |
免费 | 800篇 |
国内免费 | 36篇 |
专业分类
耳鼻咽喉 | 118篇 |
儿科学 | 324篇 |
妇产科学 | 283篇 |
基础医学 | 1526篇 |
口腔科学 | 207篇 |
临床医学 | 1020篇 |
内科学 | 2055篇 |
皮肤病学 | 130篇 |
神经病学 | 872篇 |
特种医学 | 225篇 |
外科学 | 1172篇 |
综合类 | 274篇 |
一般理论 | 9篇 |
预防医学 | 1119篇 |
眼科学 | 192篇 |
药学 | 922篇 |
中国医学 | 28篇 |
肿瘤学 | 567篇 |
出版年
2022年 | 108篇 |
2021年 | 198篇 |
2020年 | 109篇 |
2019年 | 144篇 |
2018年 | 171篇 |
2017年 | 127篇 |
2016年 | 173篇 |
2015年 | 182篇 |
2014年 | 209篇 |
2013年 | 436篇 |
2012年 | 596篇 |
2011年 | 635篇 |
2010年 | 347篇 |
2009年 | 323篇 |
2008年 | 542篇 |
2007年 | 573篇 |
2006年 | 553篇 |
2005年 | 533篇 |
2004年 | 512篇 |
2003年 | 480篇 |
2002年 | 515篇 |
2001年 | 259篇 |
2000年 | 203篇 |
1999年 | 206篇 |
1998年 | 101篇 |
1997年 | 114篇 |
1996年 | 111篇 |
1995年 | 94篇 |
1994年 | 74篇 |
1993年 | 68篇 |
1992年 | 162篇 |
1991年 | 140篇 |
1990年 | 124篇 |
1989年 | 109篇 |
1988年 | 124篇 |
1987年 | 125篇 |
1986年 | 114篇 |
1985年 | 100篇 |
1984年 | 95篇 |
1983年 | 91篇 |
1982年 | 77篇 |
1981年 | 88篇 |
1980年 | 74篇 |
1979年 | 75篇 |
1978年 | 61篇 |
1977年 | 54篇 |
1976年 | 62篇 |
1974年 | 63篇 |
1973年 | 55篇 |
1972年 | 60篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Durrant DE Richards J Tripathi A Kellogg GE Marchetti P Eleopra M Grisolia G Simoni D Lee RM 《Investigational new drugs》2009,27(1):41-52
Summary Colchicine site tubulin inhibitors are currently developed as vascular disrupting agents (VDAs). However, they were found
to have cardiotoxicity in clinical trials. To overcome the problem, we developed a stilbene derivative, cis-3, 4′, 5-trimethoxy-3′-aminostilbene (stilbene 5c), which is highly potent and has no bone marrow and cardiac toxicity in
mice. Here we attempt to optimize stilbene 5c using computer-based drug design and synthesize derivatives with benzimidazole
or indole group. Biological evaluation showed that they are weaker than stilbene 5c without better water solubility. Alternative
approach was thus adopted to make prodrugs of stilbene 5c. A water-soluble prodrug PD7 was synthesized by addition of a morpholino
group with carbamate linkage to the amino group of stilbene 5c. In vitro studies show that PD7 induces mitotic arrest and
disrupts microtubule similar to stilbene 5c. The cell signaling events in Cdc2, p53, Akt, and aurora kinase are similar in
cells treated with stilbene 5c, CA4 or PD7, suggesting that they share the same mechanism. Although PD7 is less effective
than stilbene 5c in vitro, the biological activity of PD7 as a single agent is similar to that of stilbene 5c. Combination
of PD7 with VEGF inhibitor bevacizumab significantly enhances the therapeutic efficacy of PD7 in mouse xenograft model. These
data suggest that PD7 could be a good candidate for further pre-clinical and clinical development as a new VDA for cancer
therapy. 相似文献
952.
Richard Hallinan Séverine Crettol Kingsley Agho John Attia Jacques Besson Marina Croquette-Krokar Robert Hämmig Jean-Jacques Déglon Andrew Byrne John Ray Andrew A. Somogyi Chin B. Eap 《European journal of clinical pharmacology》2009,65(11):1113-1120
Purpose
To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics.Methods
Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose.Results
Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14–16% and 17–25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4.Conclusion
Cannabis use and higher methadone doses in MMT could in part be a response to—or a cause of—more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT. 相似文献953.
Cook RT Schlueter AJ Coleman RA Tygrett L Ballas ZK Jerrells TR Nashelsky MB Ray NB Haugen TH Waldschmidt TJ 《Alcoholism, clinical and experimental research》2007,31(10):1746-1758
BACKGROUND: The well-known immune deficiency of the chronic alcoholic dictates the need for a long-term rodent ethanol administration model to evaluate the baseline immunologic effects of chronic ethanol abuse, and investigate the genetic determinants of those effects. Much published work with rodents has shown clearly that acute ethanol administration and short-term ethanol-containing liquid diets both cause elevated corticosterone and can cause significant thymocyte, pre-B cell and peripheral lymphocyte losses. Such losses may mask more subtle alterations in immune homeostasis, and in any case are generally short-lived compared with the span of chronic ethanol abuse. Thus, it is important to have a model in which long-term immune alterations can be studied free of corticosteroid-induced cell losses. METHODS: We have utilized chronic 20% (w/v) ethanol in water administration to several mouse strains for prolonged periods of time and evaluated serum corticosterone, immunologic stress parameters, and other organ changes by standard methods. RESULTS: We now confirm earlier reports that chronic ethanol in water administration to mice does not produce net elevations of corticosterone, although diurnal variation is altered. Importantly, there is neither selective loss of immune cell populations known to be corticosteroid sensitive, CD4+CD8+ thymocytes and pre-B cells, nor are changes observed in the histologic appearance of the thymus. Nonetheless, there are significant chronic ethanol effects in other tissues, including reduced heart weight, mild hepatic steatosis, alterations of gut flora, increased serum peptidoglycan, and as published elsewhere, immune system abnormalities. CONCLUSIONS: This model of ethanol administration is convenient, sustainable for up to 1 year, demonstrably feasible in several mouse strains, permits good weight gains in most strains, and results in significant changes in a number of organs. The administration method also will permit modeling of long-term steady abuse punctuated by major binges, and is suitable for supplementation studies using water soluble additives. Overall, the method is useful for a wide range of studies requiring a chronic low-stress method of ethanol administration. 相似文献
954.
955.
OBJECTIVE: Leukocyte recruitment to inflammatory sites is a prominent feature of acute and chronic inflammation. Instrumental in this process is the coordinated upregulation of leukocyte integrins (among which alpha4beta1 and beta2 integrins are major players) and their cognate receptors in inflamed tissues. To avoid the ambiguity of previous short-term antibody-based studies and to allow for long-term observation, we used genetically deficient mice to compare roles of alpha4 and beta2 integrins in leukocyte trafficking. MATERIALS AND METHODS: Aseptic peritonitis was induced in alpha4 or beta2 integrin-deficient (conditional and conventional knockouts, respectively) and control mice, and recruitment of major leukocyte subsets to the inflamed peritoneum was followed for up to 4 days. RESULTS: Despite normal chemokine levels in the peritoneum and adequate numbers, optimal recruitment of myeloid cells was impaired in both alpha4- and beta2-deficient mice. Furthermore, clearance of recruited neutrophils and macrophages was delayed in these mice. Lymphocyte migration to the peritoneum in the absence of alpha4 integrins was drastically decreased, both at steady state and during inflammation, a finding consistent with impaired lymphocyte in vitro adhesion and signaling. By contrast, in the absence of beta2 integrins, defects in lymphocyte recruitment were only evident when peritonitis was established. CONCLUSIONS: Our data with concurrent use of genetic models of integrin deficiency reveal nonredundant functions of alpha4 integrins in lymphocyte migration to the peritoneum and further refine specific roles of alpha4 and beta2 integrins concerning trafficking and clearance of other leukocyte subsets at homeostasis and during inflammation. 相似文献
956.
Fair RC 《Experimental aging research》2007,33(1):37-57
Rates of decline are estimated using record bests by age for chess and for various track and field, road running, and swimming events. Using a fairly flexible functional form, the estimates show linear percent decline between age 35 and about age 70 and then quadratic decline after that. Chess shows much less decline than the physical activities. Rates of decline are generally larger for the longer distances, and for swimming they are larger for women than for men. An advantage of using best-performance records to estimate rates of decline is that the records are generally based on very large samples. In addition, the age range is large. In this study the age range is 35 to 100 for swimming, 35 to 98 for track and field and running, and 35 to 94 for chess. The estimates also do not suffer from traditional forms of selection bias. 相似文献
957.
958.
959.
Weiss RD Griffin ML Kolodziej ME Greenfield SF Najavits LM Daley DC Doreau HR Hennen JA 《The American journal of psychiatry》2007,164(1):100-107
OBJECTIVE: Although bipolar disorder and substance use disorder frequently co-occur, there is little information on the effectiveness of behavioral treatment for this population. Integrated group therapy, which addresses the two disorders simultaneously, was compared with group drug counseling, which focuses on substance use. The authors hypothesized that patients receiving integrated group therapy would have fewer days of substance use and fewer weeks ill with bipolar disorder. METHOD: A randomized controlled trial compared 20 weeks of integrated group therapy or group drug counseling with 3 months of posttreatment follow-up. Sixty-two patients with bipolar disorder and current substance dependence, treated with mood stabilizers for >or=2 weeks, were randomly assigned to integrated group therapy (N=31) or group drug counseling (N=31). The primary outcome measure was the number of days of substance use. The primary mood outcome was the number of weeks ill with a mood episode. RESULTS: Intention-to-treat analysis revealed significantly fewer days of substance use for integrated group therapy patients during treatment and follow-up. Groups were similar in the number of weeks ill with bipolar disorder during treatment and follow-up, although integrated group therapy patients had more depressive and manic symptoms. CONCLUSIONS: Integrated group therapy, a new treatment developed specifically for patients with bipolar disorder and substance dependence, appears to be a promising approach to reduce substance use in this population. 相似文献
960.
Non-motor symptoms are an important part of Parkinson's disease (PD) symptoms complex. They cause a significant burden on the quality of life of patients and their carers and remain a major cause of hospitalisation. Treatment of non-motor symptoms can be challenging as these symptoms are often unresponsive to conventional dopaminergic therapy. However, awareness that these symptoms are related to PD is vital as research into treatment and causation will be the cornerstone for delivering a comprehensive modern treatment for PD. 相似文献