全文获取类型
收费全文 | 3215篇 |
免费 | 239篇 |
国内免费 | 2篇 |
专业分类
3456篇 |
出版年
2023年 | 12篇 |
2022年 | 27篇 |
2021年 | 56篇 |
2020年 | 36篇 |
2019年 | 54篇 |
2018年 | 63篇 |
2017年 | 58篇 |
2016年 | 96篇 |
2015年 | 140篇 |
2014年 | 168篇 |
2013年 | 239篇 |
2012年 | 257篇 |
2011年 | 247篇 |
2010年 | 164篇 |
2009年 | 157篇 |
2008年 | 160篇 |
2007年 | 208篇 |
2006年 | 184篇 |
2005年 | 180篇 |
2004年 | 149篇 |
2003年 | 140篇 |
2002年 | 135篇 |
2001年 | 32篇 |
2000年 | 25篇 |
1999年 | 27篇 |
1998年 | 35篇 |
1997年 | 28篇 |
1996年 | 25篇 |
1995年 | 17篇 |
1994年 | 22篇 |
1993年 | 17篇 |
1992年 | 20篇 |
1991年 | 20篇 |
1990年 | 30篇 |
1989年 | 14篇 |
1988年 | 16篇 |
1987年 | 12篇 |
1986年 | 19篇 |
1985年 | 17篇 |
1984年 | 17篇 |
1983年 | 8篇 |
1982年 | 15篇 |
1981年 | 14篇 |
1980年 | 15篇 |
1979年 | 9篇 |
1978年 | 10篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1972年 | 6篇 |
1969年 | 11篇 |
排序方式: 共有3456条查询结果,搜索用时 15 毫秒
51.
Roth AL Marzola E Rizzi A Arduin M Trapella C Corti C Vergura R Martinelli P Salvadori S Regoli D Corsi M Cavanni P Caló G Guerrini R 《The Journal of biological chemistry》2006,281(30):20809-20816
Neuropeptide S (NPS) has been recently recognized as the endogenous ligand for the previous orphan G-protein-coupled receptor GPR154, now referred to as the NPS receptor (NPSR). The NPS-NPSR receptor system regulates important biological functions such as sleeping/wakening, locomotion, anxiety, and food intake. To collect information on the mechanisms of interaction between NPS and its receptor, a classical structure-activity relationship study was performed. Human (h) NPS derivatives obtained by Ala and d-scan and N- and C-terminal truncation were assessed for their ability to stimulate calcium release in HEK293 cells expressing the human recombinant NPSR. The results of this study indicate that (i) the effect of hNPS is mimicked by the fragment hNPS-(1-10); (ii) Phe(2), Arg(3), and Asn(4) are crucial for biological activity; (iii) the sequence Thr(8)-Gly(9)-Met(10) is important for receptor activation, although with non-stringent chemical requirements; and (iv) the sequence Val(6)-Gly(7) acts as a hinge region between the two above-mentioned domains. However, the stimulatory effect of hNPS given intracerebroventricularly on mouse locomotor activity was not fully mimicked by hNPS-(1-10), suggesting that the C-terminal region of the peptide maintains importance for in vivo activity. In conclusion, this study identified the amino acid residues of this peptide most important for receptor activation. 相似文献
52.
Dondero F Jonsson H Rebelo M Pesce G Berti E Pons G Viarengo A 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2006,143(2):150-157
Amoebic Dictyostelium discoideum cells were employed in a bioassay to evaluate stress responses after exposures to the polyaromatic hydrocarbon benzo[a]pyrene (B[a]P) and two heavy metals (copper and mercury). Furthermore, we developed a recombinant cell line expressing a labile Green Fluorescent Protein (GFP) variant expressed under the control of an actin promoter to monitor stress-related protein degradation. Finally, cell viability was monitored to discriminate lethal exposure concentrations. The results demonstrated that exposure to sub-micromolar concentrations of mercury rendered significant changes in all studied physiological parameters, whereas B[a]P became toxic at low micromolar, and copper at high micromolar concentrations. Exposure to 0.5 microM mercury significantly reduced lysosomal membrane stability (LMS), endocytosis rate, GFP expression, and further resulted in the elevation of cytosolic free Ca(2+) ([Ca(2+)](i)). LMS in mercury-treated cells that had been pre-incubated with a specific Ca(2+)-dependent phospholipase A2 blocking agent was however not affected by the exposure, indicating that the toxic action of mercury is linked to the activation of phospholipase A2 via a Ca(2+)-signaling pathway. Exposure to 20 microM B[a]P significantly reduced LMS, endocytosis rate, and GFP expression, however without affecting [Ca(2+)](i), suggesting a calcium-independent route of toxicity for this compound. None of the physiological parameters were significantly affected by copper exposure at concentrations <400 microM, demonstrating a high resistance to this metal. Our results further showed that neither cell growth nor viability was affected by concentrations altering the studied physiological parameters. LMS, endocytosis rate, and [Ca(2+)](I), therefore, appear sensitive biomarkers of pollutant-related stress in amoebic cells. 相似文献
53.
54.
Ann H. Klopp Lara Lacerda Anshul Gupta Bisrat G. Debeb Travis Solley Li Li Erika Spaeth Wei Xu Xiaomei Zhang Michael T. Lewis James M. Reuben Savitri Krishnamurthy Mauro Ferrari Rogério Gaspar Thomas A. Buchholz Massimo Cristofanilli Frank Marini Michael Andreeff Wendy A. Woodward 《PloS one》2010,5(8)
Introduction
Normal and malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew, referred to as stem cells, or tumor initiating cells (TIC). These cells can be enriched by growth as “mammospheres” in three-dimensional cultures.Objective
We tested the hypothesis that human bone-marrow derived mesenchymal stem cells (MSC), which are known to support tumor growth and metastasis, increase mammosphere formation.Results
We found that MSC increased human mammary epithelial cell (HMEC) mammosphere formation in a dose-dependent manner. A similar increase in sphere formation was seen in human inflammatory (SUM149) and non-inflammatory breast cancer cell lines (MCF-7) but not in primary inflammatory breast cancer cells (MDA-IBC-3). We determined that increased mammosphere formation can be mediated by secreted factors as MSC conditioned media from MSC spheroids significantly increased HMEC, MCF-7 and SUM149 mammosphere formation by 6.4 to 21-fold. Mammospheres grown in MSC conditioned media had lower levels of the cell adhesion protein, E-cadherin, and increased expression of N-cadherin in SUM149 and HMEC cells, characteristic of a pro-invasive mesenchymal phenotype. Co-injection with MSC in vivo resulted in a reduced latency time to develop detectable MCF-7 and MDA-IBC-3 tumors and increased the growth of MDA-IBC-3 tumors. Furthermore, E-cadherin expression was decreased in MDA-IBC-3 xenografts with co-injection of MSC.Conclusions
MSC increase the efficiency of primary mammosphere formation in normal and malignant breast cells and decrease E-cadherin expression, a biologic event associated with breast cancer progression and resistance to therapy. 相似文献55.
Zinc nutritional status and its relationships with hyperinsulinemia in obese children and adolescents 总被引:4,自引:0,他引:4
A perturbation of zinc metabolism has been noted in subjects with obesity. The present work intends to investigate whether
the zinc nutritional status is associated with hyperinsulinemia in obesity. A study was carried out in a group of obese children
and adolescents (n=23) and compared to a control group (n=21), both between 7 and 14 yr of age. Software analyzed diet information from 3-d food records. Body composition was evaluated
by body mass index (BMI), bioelectrical impedance, and skinfold measurements. Zinc nutritional status was evaluated by Zn
determination in plasma, erythrocyte, and 24-h urine, by atomic absorption spectrophotometry (λ=213.9 nm). Insulin was measured
by radioimmunoassay (Linco Res). Diets consumed by both groups had marginal concentrations of zinc. Zinc concentrations in
plasma and erythrocytes were significantly lower in the obese group. Urinary zinc excretion and serum insulin were significantly
higher in the same group, although the insulinemia and the parameters of zinc nutritional status were not significantly correlated.
As a result, considering that zinc is part of the synthesis and secretion of this hormone, an assessment is necessary of the
possible participation of the oligoelement in the mechanisms of insulin resistance, commonly present in obese patients. 相似文献
56.
Iron deficiency can have nonhematological manifestations, some of which may affect the gastrointestinal tract. The aim of
this study was to determine if iron-deficiency anemia in growing rats affected small-bowel permeability as assessed by the
urinary ratio of lactulose and mannitol. Thirty-seven male Harlan Sprague-Dawley rats (21 d of age) were randomly divided
into two groups and fed either an iron-deficient (n=19) or an iron-sufficient diet (n=18) that contained either 13.5 or 43.8 mg of iron/kg diet, respectively. Animals were evaluated between 25 and 38 d of dietary
treatment. Intestinal permeability was assessed by measuring the lactulose/mannitol urinary ratio following administration
of a solution that contained the two sugars. At the end of the study, the mean body weight of rats fed the low-iron diet was
approx 95% that of the controls. The mean hemoglobin (g/dL) was significantly lower in the low-iron diet group (11.2±1.4)
than in the control group (16.9±0.8) (p=0.001). The liver iron concentration (μg/g) of the anemic group (41.4±4.7) was also statistically (p=0.001) lower than in the control group (116.6±18.2). The lactulose/mannitol ratio was lower in the anemic rats (2.0±0.7)
than in the control group (2.6±0.7) (p=0.008), a finding that is not suggestive of intestinal mucosal atrophy, previously described in anemic children. 相似文献
57.
E Ricciardi M Jakimovska P Maniglio M Schimberni A Frega B Kobal M Moscarini 《World journal of surgical oncology》2012,10(1):177
ABSTRACT: BACKGROUND: Intraoperative injury of the obturator nerve has rarely been reported in patients with gynecological malignancies undergoing extensive radical surgeries. Irreversible damage of this nerve causes thigh paresthesia and claudication. Intraoperative repair may be done by end-to-end anastomosis or grafting when achieving tension-free anastomosis is not possible. CASE PRESENTATION: A 28-year-old woman with stage IB cervical cancer underwent fertility--sparing surgery, including conization and bilateral pelvic lymphadenectomy. The left obturator nerve was damaged intraoperatively during pelvic dissection. CONCLUSION: Immediate laparoscopic repair was successful and there was no functional deficit in the left thigh for six months postoperatively. 相似文献
58.
59.
AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Detailed Analysis of the Humoral Immune Response to a Protective Vaccine 总被引:1,自引:0,他引:1 下载免费PDF全文
60.