全文获取类型
收费全文 | 325篇 |
免费 | 25篇 |
国内免费 | 24篇 |
专业分类
儿科学 | 27篇 |
妇产科学 | 4篇 |
基础医学 | 18篇 |
口腔科学 | 8篇 |
临床医学 | 38篇 |
内科学 | 82篇 |
皮肤病学 | 5篇 |
神经病学 | 17篇 |
特种医学 | 44篇 |
外科学 | 22篇 |
综合类 | 40篇 |
预防医学 | 10篇 |
眼科学 | 5篇 |
药学 | 35篇 |
肿瘤学 | 19篇 |
出版年
2022年 | 3篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 10篇 |
2013年 | 13篇 |
2012年 | 4篇 |
2011年 | 5篇 |
2010年 | 14篇 |
2009年 | 14篇 |
2008年 | 9篇 |
2007年 | 19篇 |
2006年 | 8篇 |
2005年 | 4篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 8篇 |
2001年 | 11篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 21篇 |
1997年 | 19篇 |
1996年 | 19篇 |
1995年 | 9篇 |
1994年 | 20篇 |
1993年 | 11篇 |
1992年 | 6篇 |
1991年 | 10篇 |
1990年 | 4篇 |
1989年 | 11篇 |
1988年 | 16篇 |
1987年 | 5篇 |
1986年 | 9篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有374条查询结果,搜索用时 15 毫秒
81.
Leucocyte membrane expression of proteinase 3 correlates with disease activity in patients with Wegener's granulomatosis 总被引:3,自引:0,他引:3
Wegener's granulomatosis (WG) is an inflammatory disorder characterized by
granulomatous inflammation and vasculitis, and is strongly associated with
antineutrophil cytoplasmic antibodies (ANCA). ANCA in patients with WG are
directed against proteinase 3 (Pr3) in most of the cases. In vitro, upon
neutrophil priming, ANCA antigens are expressed on the cell surface,
thereby becoming available for interaction with ANCA. Subsequently, these
neutrophils become activated. Since ANCA can only interact with leucocytes
when the ANCA antigens are present on the cell surface, we questioned
whether Pr3 is already expressed on the membranes of circulating
granulocytes and monocytes of patients with WG, and whether Pr3 expression
is related to disease activity, so explaining the systemic nature and
severity of the disease. The expression of Pr3, and other ANCA antigens,
i.e. myeloperoxidase (MPO) and human leucocyte elastase (HLE), was analysed
on circulating granulocytes and monocytes by flow cytometry, using a
non-activating whole-blood method. Disease activity was quantitated using
the Birmingham Vasculitis Activity Score (BVAS). Seventeen patients with
active WG and anti-Pr3 antibodies were included in this study. Nine of
these patients were also analysed at the time of remission. Twelve patients
with sepsis served as positive controls, and 10 healthy volunteers as
negative controls for granulocyte/monocyte activation. Pr3 expression on
neutrophils was increased in patients with active WG compared to patients
with quiescent disease and healthy controls. On monocytes, no differences
in Pr3 expression were found between those groups. Furthermore, the
expression of MPO and HLE did not differ between patient groups and healthy
controls. Upon follow-up, the expression of Pr3 on neutrophils from
patients with active WG decreased when patients went into remission. Pr3
expression on neutrophils correlated with the BVAS score (r = 0.40, P <
0.05). In conclusion, circulating neutrophils from patients with active WG
have increased expression of Pr3. In addition, the expression of Pr3
correlates with disease activity, suggesting that the availability of Pr3
for interaction with ANCA plays a central role in the disease process.
相似文献
82.
Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone.
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
P K Pang R Wang J Shan E Karpinski C G Benishin 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(2):623-627
The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca2+ channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca2+ currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca2+ channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca2+ in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues, PTH can act as an endogenous blocker of Ca2+ entry. 相似文献
83.
A 21-year-old woman presented with acute onset of upper abdominal pain. A diagnosis of Peutz-Jeghers syndrome (PJS) was made based on the clinical picture of perioral pigmentation with imaging findings of transient jejunojejunal intussusceptions and small bowel polyps, and confirmed by characteristic histopathological appearances of Peutz-Jeghers polyps. PJS is a rare hereditary condition characterised by unique hamartomatous polyps, perioral mucocutaneous pigmentations, and increased susceptibility to gastrointestinal and extraintestinal neoplasms. Patients usually present with recurrent abdominal pain due to intussusception caused by polyps. Other modes of presentations include rectal bleeding and melaena. We describe the imaging findings of PJS and provide a brief review of bowel polyposis syndromes. The latter are relatively rare disorders characterised by multiple polyps in the large or small intestine, with associated risk of malignancies and other extraintestinal manifestations. Awareness of the manifestations and early diagnosis of these syndromes is crucial to prevent further complications. 相似文献
84.
The purine metabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are important in lymphocyte differentiation, and genetic deficiencies of either enzyme have been associated with hereditary immunodeficiency states. Both ADA and PNP activity were measured in null cell-enriched and T cell-enriched peripheral blood lymphocytes from 16 patients with the acquired immune deficiency syndrome (AIDS), seven patients with the AIDS-related symptom complex (ARC), and seven asymptomatic homosexuals. ADA activity in nmol/10(6) lymphocytes/h was significantly elevated in null lymphocytes from AIDS (161 +/- 12) as compared with 23 healthy heterosexual controls (127 +/- 8;P less than .025). PNP activity was also significantly increased in null lymphocytes from AIDS patients (96 +/- 10;P less than .005) as well as those from ARC patients (84 +/- 11:P less than .025) relative to controls (61 +/- 5). No significant differences in enzyme activity were noted in T cell-enriched cells in any group. Along with elevated enzyme activity, AIDS patients had small yet significant increases in the percentages of HLA-DR (P less than .025), terminal deoxynucleotidyl transferase (TdT) (P less than .0001), and peanut agglutinin receptor (P less than .0001) positive lymphocytes in the null fraction compared with controls. TdT-positive cells appeared morphologically as large lymphoblasts with irregular nuclei. The data imply that the cellular immune deficiency in AIDS is not a result of deficiencies in lymphocyte ADA or PNP activity, but is more likely associated with an increase in an immature and/or activated lymphocyte subset. 相似文献
85.
Purification and properties of bacterially synthesized human granulocyte-macrophage colony stimulating factor 总被引:16,自引:0,他引:16
Burgess AW; Begley CG; Johnson GR; Lopez AF; Williamson DJ; Mermod JJ; Simpson RJ; Schmitz A; DeLamarter JF 《Blood》1987,69(1):43-51
Human granulocyte-macrophage colony stimulating factor (GM-CSF) has been synthesized in high yield using a temperature inducible plasmid in Escherichia coli. The human GM-CSF is readily isolated from the bacterial proteins because of its differential solubility and chromatographic properties. The bacterially synthesized form of the human GM-CSF contains an extra methionine residue at position 1, but otherwise it is identical to the polypeptide predicted from the cDNA sequence. The specific activity of 2.9 X 10(7) units/mg of protein for purified bacterially synthesized human GM-CSF indicates that despite the lack of glycosylation, the molecule is substantially in its native conformation. This molecule stimulated the same number and type of both seven- and 14-day human bone marrow colonies as the CSF alpha preparation from human placental conditioned medium. Human GM-CSF had no activity on murine bone marrow or murine leukemic cells. There was no detectable, direct stimulation of adult human erythroid burst forming units (BFU-E) by the bacterially synthesized human GM-CSF. Although impure preparations containing native human GM-CSF (eg, human placental conditioned medium) stimulated the formation of mixed colonies, even in the presence of erythropoietin, the bacterially synthesized human GM-CSF failed to stimulate the formation of mixed colonies from adult human bone marrow cells. The bacterially synthesized human GM-CSF increased N-formyl-methionyl-leucyl- phenylalanine (FMLP)-induced superoxide production and lysozyme secretion. Antibody-dependent cytotoxicity and phagocytosis by human neutrophils was stimulated by the bacterially synthesized human GM-CSF and eosinophils were also activated in the antibody-dependent cytotoxicity assay. 相似文献
86.
KA Jackman AA Miller TM De Silva PJ Crack GR Drummond CG Sobey 《British journal of pharmacology》2009,156(4):680-688
Background and purpose:
Reactive oxygen species (ROS) derived from Nox2-containing reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity is reportedly detrimental in cerebrovascular disease. However, ROS generation by other Nox isoforms may have a physiological role. No Nox2-selective inhibitors have yet been identified, and thus it is unclear whether isoform non-selective Nox inhibitors would necessarily improve outcome after stroke. We assessed the effect of apocynin on cerebrovascular ROS production and also on outcome following cerebral ischaemia when administered either before ischaemia or after cerebral reperfusion. The involvement of Nox2-containing NADPH oxidase in the effects of apocynin was assessed using Nox2−/− mice.Experimental approach:
Transient cerebral ischaemia was induced by 0.5 h middle cerebral artery occlusion followed by 23.5 h reperfusion. Mice received apocynin (2.5 mg·kg−1, i.p.) either 0.5 h before ischaemia or 1 h after reperfusion. In situ superoxide production after cerebral ischaemia-reperfusion was measured in brain sections of wild-type mice at 24 h using dihydroethidium fluorescence.Key results:
Treatment with apocynin 0.5 h before ischaemia reduced total infarct volume, neurological impairment and mortality in wild-type but not Nox2−/− mice. Conversely, treatment with apocynin 1 h after initiation of reperfusion had no protective effect. Cerebral ischaemia and reperfusion increased superoxide production in the brain at 24 h, and pretreatment but not posttreatment with apocynin reduced superoxide levels.Conclusions and implications:
Apocynin improves outcome following stroke when administered before ischaemia in wild-type but not Nox2−/− mice. 相似文献87.
Bisphosphonate associated osteonecrosis of the jaws (ONJ) usually commences at the alveolus. Comparison is made between the structure and function of long bones and alveolar bone and the differing susceptibilities of the bisphosphonates at these different sites are explored. Current concepts of the causation of ONJ are discussed. The clinical implications of these findings to dentists managing periodontal conditions are presented. 相似文献
88.
Sloley BD Pang PK Huang BH Ba F Li FL Benishin CG Greenshaw AJ Shan JJ 《Journal of psychiatry & neuroscience : JPN》1999,24(5):442-452
OBJECTIVE: To determine if HT-1001, an extract of American ginseng, affects scopolamine-induced memory and performance deficits in a spatial learning task, alters brain concentrations of aminergic neurotransmitters, and alters choline uptake in synaptosome preparations. DESIGN: Animal study. ANIMALS: 48 Sprague Dawley rats. INTERVENTIONS: Long-term oral administration of a test material or control solution. Intraperitoneal administration of scopolamine (2 mg/kg) 30 minutes before testing. OUTCOME MEASURES: Performance on Morris water maze task, choline uptake, aminergic neurotransmitter analysis, in vitro monoamine oxidase analysis (of compounds). RESULTS: HT-1001 protected against scopolamine-induced amnesia and increased choline uptake in synaptosomal preparations. HT-1001 did not alter brain concentrations of norepinephrine, dopamine, 5-HT (serotonin), 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleactic acid. HT-1001 had a very weak ability to inhibit monoamine oxidase activity in vitro. CONCLUSIONS: HT-1001 demonstrates a capacity to protect against scopolamine-induced memory deficits. 相似文献
89.
90.
Rat ferritin-H: cDNA cloning, differential expression and localization during hepatocarcinogenesis 总被引:2,自引:0,他引:2
Wu CG; Groenink M; Bosma A; Reitsma PH; van Deventer SJ; Chamuleau RA 《Carcinogenesis》1997,18(1):47-52
Elevated serum ferritin levels, especially of the H subunit, accompany many
clinical malignancies. By using the subtraction-enhanced display technique,
we have recently isolated several cDNA clones which are over- expressed in
rat hepatocellular carcinoma induced by diethylnitrosamine. One
830-base-pair clone was 88% similar to human ferritin-H cDNA and encoded a
182 amino acid protein which is 97% homologous to human ferritin-H chain.
Hepatic mRNA levels of ferritin-H were increased markedly at the early
stage of diethylnitrosamine- induced hepatocarcinogenesis in the rat (6
weeks) and appeared more than 10-fold overexpressed as the tumour
progressed. In contrast, hepatic ferritin-H mRNA remained constant during
liver regeneration after a 70% partial hepatectomy. In situ hybridization
showed that over- expression of ferritin-H was exclusively localized to
preneoplastic foci, to tumour nodules and to tumour cells invading blood
vessels. These findings suggest that ferritin-H is a highly conserved
protein, its over-expression during tumour development is phenotypically
correlated with tumour initiation and/or progression, and it is useful as
an early marker for hepatocellular carcinoma.
相似文献