全文获取类型
收费全文 | 5598篇 |
免费 | 297篇 |
国内免费 | 25篇 |
专业分类
耳鼻咽喉 | 20篇 |
儿科学 | 160篇 |
妇产科学 | 131篇 |
基础医学 | 741篇 |
口腔科学 | 94篇 |
临床医学 | 338篇 |
内科学 | 1440篇 |
皮肤病学 | 191篇 |
神经病学 | 334篇 |
特种医学 | 197篇 |
外科学 | 1096篇 |
综合类 | 13篇 |
预防医学 | 134篇 |
眼科学 | 62篇 |
药学 | 253篇 |
中国医学 | 1篇 |
肿瘤学 | 715篇 |
出版年
2024年 | 3篇 |
2023年 | 48篇 |
2022年 | 101篇 |
2021年 | 153篇 |
2020年 | 68篇 |
2019年 | 95篇 |
2018年 | 131篇 |
2017年 | 106篇 |
2016年 | 136篇 |
2015年 | 154篇 |
2014年 | 161篇 |
2013年 | 217篇 |
2012年 | 366篇 |
2011年 | 398篇 |
2010年 | 200篇 |
2009年 | 201篇 |
2008年 | 376篇 |
2007年 | 348篇 |
2006年 | 413篇 |
2005年 | 353篇 |
2004年 | 375篇 |
2003年 | 370篇 |
2002年 | 364篇 |
2001年 | 64篇 |
2000年 | 46篇 |
1999年 | 56篇 |
1998年 | 83篇 |
1997年 | 73篇 |
1996年 | 66篇 |
1995年 | 51篇 |
1994年 | 59篇 |
1993年 | 51篇 |
1992年 | 28篇 |
1991年 | 43篇 |
1990年 | 27篇 |
1989年 | 22篇 |
1988年 | 18篇 |
1987年 | 7篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 4篇 |
1981年 | 14篇 |
1980年 | 4篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1973年 | 4篇 |
1972年 | 3篇 |
排序方式: 共有5920条查询结果,搜索用时 11 毫秒
11.
Are cytokines possible mediators of cancer cachexia? 总被引:1,自引:0,他引:1
Yoshikazu Noguchi Takaki Yoshikawa Akihiko Matsumoto Gösta Svaninger Johan Gelin 《Surgery today》1996,26(7):467-475
The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991. 相似文献
12.
Keigo Kohara Tomio Ono Keiko Tominaga-Yoshino Tomokazu Shimonaga Seiichi Kawashima Akihiko Ogura 《Brain research》1998,809(2):285
Neurons survive when their activity is maintained. An influential hypothesis on the cellular mechanism underlying this phenomenon is that there is an appropriate range of intracellular Ca2+ concentration ([Ca2+]i) for survival. The rat cerebellar granule neuron in culture serves as the most often used model system for the analysis of activity-dependent survival, since it does not survive unless an excitant (KCl or glutamate) is added to the culture medium. Against the above-mentioned hypothesis, we found in our previous examination no difference between steady-state [Ca2+]i in granule neurons cultured under high KCl (i.e., survival) and low KCl (i.e., death) conditions. In this report, we present the quantitative background of unchanged [Ca2+]i between the two culture conditions. Influx of Ca2+ due predominantly to L-type voltage-dependent calcium channels was higher in high KCl cultures than in low KCl cultures. At the same time, efflux of Ca2+ due to the activity of Ca2+/Na+ antiport was also higher in high KCl cultures. Additionally, we found that the endocytotic activity was greater in high KCl cultures than in low KCl cultures, as monitored by the rate of uptake of horseradish peroxidase added to medium. Since the uptake was blocked by an internal Ca2+ chelator, the increased endocytotic activity in high KCl cultures might be a consequence of the enhanced Ca2+ turnover. 相似文献
13.
Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia 总被引:3,自引:0,他引:3
Taketomi T Yoshiga D Taniguchi K Kobayashi T Nonami A Kato R Sasaki M Sasaki A Ishibashi H Moriyama M Nakamura K Nishimura J Yoshimura A 《Nature neuroscience》2005,8(7):855-857
We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction. Glial cell line-derived neurotrophic factor (GDNF) induced hyperactivation of ERK and Akt in enteric nerve cells. Anti-GDNF antibody administration corrected nerve hyperplasia in Sprouty2-deficient mice. We show Sprouty2 to be a negative regulator of GDNF for the neonatal development or survival of enteric nerve cells. 相似文献
14.
Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease 总被引:1,自引:0,他引:1
Castellani RJ Honda K Zhu X Cash AD Nunomura A Perry G Smith MA 《Ageing research reviews》2004,3(3):319-326
Metal-catalyzed hydroxyl radicals are potent mediators of cellular injury, affecting every category of macromolecule, and are central to the oxidative injury hypothesis of Alzheimer disease (AD) pathogenesis. Studies on redox-competent copper and iron indicate that redox activity in AD resides exclusively within the neuronal cytosol and that chelation with deferoxamine, DTPA, or, more recently, iodochlorhydroxyquin, removes this activity. We have also found that while proteins that accumulate in AD possess metal-binding sites, metal-associated cellular redox activity is primarily dependent on metals associated with nucleic acid, specifically cytoplasmic RNA. These findings indicate aberrations in iron homeostasis that, we suspect, arise primarily from heme, since heme oxygenase-1, an enzyme that catalyzes the conversion of heme to iron and biliverdin, is increased in AD, and mitochondria, since mitochondria turnover, mitochondrial DNA, and cytochrome C oxidative activity are all increased in AD. These findings, as well as studies demonstrating a reduction in microtubule density in AD neurons, suggest that mitochondrial dysfunction, acting in concert with cytoskeletal pathology, serves to increase redox-active heavy metals and initiates a cascade of abnormal events culminating in AD pathology. 相似文献
15.
Kiyoshi A Ishikawa T Hayashi K Iwatsuki Y Ishii K Nakayama K 《Pflügers Archiv : European journal of physiology》2003,447(2):142-149
Rhythmical contractions accompanied by an increase in cytosolic Ca2+ concentrations were produced in ring preparations of endothelium-denuded pulmonary arteries from monocrotaline-treated rats, but not in those from vehicle-treated rats, 2-3 h after a resting tension of 15 mN (150-180% of the initial wall length of the artery) was applied. The rhythmical contractions were abolished by nicardipine and ryanodine. Cyclopiazonic acid reduced the relaxation phase of the rhythmical contractions, finally leading to a sustained contraction. Similarly, apamin caused a sustained contraction, whereas charybdotoxin increased the amplitude of the rhythmical contractions. Glibenclamide had no apparent effects on them. Indomethacin and the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 abolished the rhythmical contractions and reduced the tension, but the thromboxane synthase inhibitor ozagrel had no effect. These results suggest that optimal stretch induces rhythmical contractions in the pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats, to which both Ca2+ influx through voltage-operated Ca2+ channels and Ca2+ release from the endoplasmic reticulum seem to contribute. It is also suggested that small-conductance Ca(2+)-activated K+ channels participate in the relaxation phase of rhythmical contractions. Furthermore, prostaglandin H2 released from nonendothelial cells is likely to play a pivotal role in the induction of rhythmical contractions. 相似文献
16.
Single nucleotide polymorphisms in the protamine-1 and -2 genes of fertile and infertile human male populations 总被引:6,自引:0,他引:6
Tanaka H Miyagawa Y Tsujimura A Matsumiya K Okuyama A Nishimune Y 《Molecular human reproduction》2003,9(2):69-73
Although various genetic factors have been implicated in human male infertility, the causative genes for the different types of idiopathic male infertility have not been elucidated. Protamines, which are the major DNA-binding proteins in the sperm nucleus, package the DNA into the sperm head. Analysis of the human protamine-1 (PRM1) and -2 (PRM2) gene sequences in 226 sterile male patients and in 270 proven-fertile male volunteers revealed four single nucleotide polymorphisms (SNPs) in the PRM1 coding region, which did not cause any amino acid substitutions, and one SNP in the PRM2 gene, which produced translation termination. We also observed one SNP in the 3' non-coding region of the PRM1 gene, and two SNPs within the intron of the PRM2 gene. The prevalence of these SNPs was similar in both infertile patients and in proven-fertile volunteers, except that the c248t alteration in the PRM2 gene induced a nonsense codon under conditions of heterozygosity in one infertile patient. Although the PRM1 and PRM2 genes are highly conserved, the single SNP in the PRM2 gene that induces translation termination may result in male infertility due to haploinsufficiency of PRM2. 相似文献
17.
18.
The effects of hyperbaric exposure with high oxygen concentration on spinal motoneurons and the skeletal muscle fibers that they innervate were investigated. Five-week-old male rats were exposed to a hyperbaric (1.25 atmospheric pressure) environment with a high oxygen concentration (35.0%) for 6h daily. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were examined after 8 weeks of hyperbaric exposure. In addition, the fiber type distribution, cell size, and oxidative enzyme activity of the slow soleus and fast plantaris muscles were examined. The oxidative enzyme activity of alpha motoneurons innervating the soleus and plantaris muscles increased after hyperbaric exposure, irrespective of their cell body sizes. The percentage of high-oxidative fibers in the soleus and plantaris muscles increased after hyperbaric exposure. The oxidative enzyme activity of all types of fibers in the soleus and plantaris muscles increased after hyperbaric exposure. It is concluded that hyperbaric exposure with high oxygen concentration enhances the oxidative capacity of neuromuscular units. 相似文献
19.
20.
Temperature-responsive culture dishes immobilized with insulin have been fabricated and studied to shorten cell culture periods by facilitating more rapid cell proliferation. Cells are recovered as contiguous cell sheets simply by temperature changes. Functionalized culture dishes were prepared by previously reported electron beam grafting copolymerization of N-isopropylacrylamide (IPAAm) with its carboxylate-derivatized analog, 2-carboxyisopropylacrylamide (CIPAAm), having similar molecular structure to IPAAm but with carboxylate side chains to tissue culture polystyrene dishes. Insulin was then immobilized onto culture dishes through standard amide bond formation with CIPAAm carboxylate groups. Adhesion and proliferation of bovine carotid artery endothelial cells (ECs) were examined on these insulin-immobilized dishes. Insulin immobilization was shown to promote cell proliferation in serum-supplemented medium. Increasing the grafted CIPAAm content on the tissue culture surfaces reduces cell adhesion and proliferation, even though these surfaces contained increased amounts of immobilized insulin. This result implies that a discrete balance exists between the amount of CIPAAm-free carboxylate groups and immobilized insulin for optimum cell proliferative stimulation. Cells grown on the insulin-immobilized surfaces can be recovered as contiguous cell monolayers simply by lowering culture temperature, without need for exogenous enzyme or calcium chelator additions. In conclusion, insulin-modified thermoresponsive culture dishes may prove useful for advanced cell culture and tissue engineering applications since they facilitate cell proliferation, and cultured cells can be recovered as viable contiguous monolayers by merely reducing culture temperature. 相似文献