全文获取类型
收费全文 | 579篇 |
免费 | 36篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 42篇 |
妇产科学 | 1篇 |
基础医学 | 50篇 |
口腔科学 | 35篇 |
临床医学 | 53篇 |
内科学 | 125篇 |
皮肤病学 | 18篇 |
神经病学 | 10篇 |
特种医学 | 99篇 |
外科学 | 63篇 |
综合类 | 24篇 |
预防医学 | 34篇 |
眼科学 | 5篇 |
药学 | 45篇 |
中国医学 | 1篇 |
肿瘤学 | 15篇 |
出版年
2021年 | 15篇 |
2020年 | 4篇 |
2019年 | 1篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 12篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 28篇 |
2012年 | 24篇 |
2011年 | 10篇 |
2010年 | 26篇 |
2009年 | 27篇 |
2008年 | 14篇 |
2007年 | 11篇 |
2006年 | 20篇 |
2005年 | 15篇 |
2004年 | 11篇 |
2003年 | 14篇 |
2002年 | 11篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 19篇 |
1998年 | 36篇 |
1997年 | 25篇 |
1996年 | 23篇 |
1995年 | 13篇 |
1994年 | 23篇 |
1993年 | 23篇 |
1992年 | 13篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 15篇 |
1988年 | 17篇 |
1987年 | 9篇 |
1986年 | 16篇 |
1985年 | 7篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 12篇 |
1980年 | 12篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 10篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1957年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有622条查询结果,搜索用时 15 毫秒
81.
Cuello C; Palladinetti P; Tedla N; Di Girolamo N; Lloyd AR; McCluskey PJ; Wakefield D 《Rheumatology (Oxford, England)》1998,37(7):779-783
OBJECTIVE: To investigate the expression and source of chemokines in minor
salivary gland biopsies (MSGs) in patients with Sjogren's syndrome (SS).
METHODS: Immunohistochemical analysis was used to determine the pattern of
chemokine expression in MSGs from patients with (n=6) and without (n=5) SS,
as well as to examine the phenotype of both resident and infiltrating cells
expressing chemokines. RESULTS: Significant differences in the number of
infiltrating mononuclear (MN) cells in patients with and without SS were
noted. Ductal epithelial cells of SS biopsies expressed significantly
increased levels of macrophage inflammatory protein (MIP)-1alpha,
MIP-1beta, interleukin-8 (IL-8) and RANTES (Regulated upon Activation,
Normal T cell Expressed and Secreted). Biopsies from patients with SS
showed that MIP-1beta was expressed by 51% of infiltrating cells, while 41%
expressed MIP-1alpha, whereas 22 and 7% expressed RANTES and IL-8,
respectively. CONCLUSION: Chemokines expressed by ductal epithelial cells
may attract circulating leucocytes, in particular CD4+ T cells, towards the
site of inflammation, thereby orchestrating the influx of MN cells
characteristically seen in MSGs in SS. Chemokines may be induced directly
by a putative triggering agent for SS, or secondary to the release of
pro-inflammatory cytokines produced by epithelial cells. These findings
further implicate epithelial cells as playing a major role in the
pathogenesis of SS and implicate chemokines in the leucocyte recruitment in
this setting.
相似文献
82.
83.
Spinning top urethra (STU) is a term used to describe a widened posterior urethra seen mainly in girls. It is commonly regarded as a normal variant. The authors studied 30 girls with STU using videourodynamics. Twenty-eight showed bladder instability; 21, a congenital wide bladder neck anomaly; and 20, both instability and a wide bladder neck. One patient had a sensitive bladder. All patients had a urodynamic abnormality. The authors believe that the STU is nearly always an indication of bladder instability or wide bladder neck anomaly. The most common mechanism for the dilatation of the posterior urethra is that unstable contractions are resisted by a voluntary increase in distal sphincter tension so as to prevent leakage of urine. The resulting pressure rise produces distention of the posterior urethra, which will be maximal in subjects with a weak bladder neck mechanism as in the congenital wide bladder neck anomaly. The authors believe that STU is seldom if ever a normal variant. 相似文献
84.
The platelet release reaction was studied by a new quenched-flow approach. Platelets labeled with 14C-serotonin were reacted for short times (up to 5 sec) with thrombin and then quenched with glutaraldehyde or paraformaldehyde. Serotonin secretion began within 1 sec and was nearly complete by 4 sec. Aggregation recorded by a resistive-particle counter was similarly fast. Therefore, the quenched-flow system reveals that serotonin secretion can occur more rapidly than estimated in earlier studies. 相似文献
85.
Andi Utama Sigit Purwantomo Marlinang Diarta Siburian Rama Dhenni Rino Alvani Gani Irsan Hasan Andri Sanityoso Upik Anderiani Miskad Fardah Akil Irawan Yusuf Wenny Astuti Achwan Soewignjo Soemohardjo Syafruddin AR Lelosutan Ruswhandi Martamala Benyamin Lukito Unggul Budihusodo Laurentius Adrianus Lesmana Ali Sulaiman Susan Tai 《World journal of gastroenterology : WJG》2009,15(32):4028-4036
AIM: To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia.
METHODS: Patients with chronic hepatitis (CH, n =61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.
RESULTS: HBV genotype B (subgenotypes B2, B3, B4, 85 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis.
CONCLUSION: HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease. 相似文献
METHODS: Patients with chronic hepatitis (CH, n =61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.
RESULTS: HBV genotype B (subgenotypes B2, B3, B4, 85 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis.
CONCLUSION: HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease. 相似文献
86.
G Zifarelli A Liantonio A Gradogna A Picollo G Gramegna M De Bellis AR Murgia E Babini D Conte Camerino M Pusch 《British journal of pharmacology》2010,160(7):1652-1661
Background and purpose:
ClC-K kidney Cl− channels are important for renal and inner ear transepithelial Cl− transport, and are potentially interesting pharmacological targets. They are modulated by niflumic acid (NFA), a non-steroidal anti-inflammatory drug, in a biphasic way: NFA activates ClC-Ka at low concentrations, but blocks the channel above ∼1 mM. We attempted to identify the amino acids involved in the activation of ClC-Ka by NFA.Experimental approach:
We used site-directed mutagenesis and two-electrode voltage clamp analysis of wild-type and mutant channels expressed in Xenopus oocytes. Guided by the crystal structure of a bacterial CLC homolog, we screened 97 ClC-Ka mutations for alterations of NFA effects.Key results:
Mutations of five residues significantly reduced the potentiating effect of NFA. Two of these (G167A and F213A) drastically altered general gating properties and are unlikely to be involved in NFA binding. The three remaining mutants (L155A, G345S and A349E) severely impaired or abolished NFA potentiation.Conclusions and implications:
The three key residues identified (L155, G345, A349) are localized in two different protein regions that, based on the crystal structure of bacterial CLC homologs, are expected to be exposed to the extracellular side of the channel, relatively close to each other, and are thus good candidates for being part of the potentiating NFA binding site. Alternatively, the protein region identified mediates conformational changes following NFA binding. Our results are an important step towards the development of ClC-Ka activators for treating Bartter syndrome types III and IV with residual channel activity. 相似文献87.
TG Bird L Boutler A Cole S Lorenzini WY Lu T Hay R Ridgway M Williams B Knight S Gordon Keylock D Wjotacha T Jamieson JP Iredale AR Clarke OJ Sansom SJ Forbes 《Lancet》2013
Insufficient regeneration of the adult liver is believed to cause failure to recover from severe liver disease. An undifferentiated cell population with stem-cell-like qualities known as hepatic progenitor cells (HPCs) is hypothesised to have a central role in regeneration of the adult liver during massive or chronic liver disease. Stem cells in other organ systems are believed to reside in a specialised microenvironment or niche that supports their maintenance and function. The existence of a hepatic stem cell niche might provide a means of therapeutically manipulating endogenous HPCs in vivo as a regenerative therapy.To investigate the physiological potential of HPCs to regenerate the mammalian liver, we have established a novel model of hepatocellular injury and HPC activation using genetic manipulation of hepatocytes. After hepatocyte senescence and death in this model (AhCre Mdm2flox), HPCs expand and bring about the complete regeneration of the liver parenchyma.We demonstrate that a stereotypical niche, consisting partly of macrophages, exists in both animal models and correlating human disease. Using cell tracking, we show active recruitment of extrahepatic macrophages into this niche during injury. In health, intravenous injection of macrophages results in macrophage engraftment to the liver niche, with subsequent HPC activation and changes to liver structure and function.Within the niche, macrophages use paracrine signalling to control both HPC proliferation and cell fate via TWEAK (tumour-necrosis-factor-like weak inducer of apoptosis) and the Wnt signalling pathway, respectively. After hepatocellular injury, macrophages ingest hepatocyte debris, and release Wnt which promotes HPC differentiation into hepatocytes. TWEAK is vital for HPC proliferation in the AhCre Mdm2flox model of regeneration. Here, the absence of TWEAK signalling results in liver failure and mortality.This work has demonstrated for the first time the ability of a solid organ to fully regenerate in the adult mammal from progenitor cells, and additionally highlights mechanisms by which this process can be modulated by either small molecule or cell therapy.FundingUniversity of Edinburgh. 相似文献
88.
R Alexander A Kerby AA Aubdool AR Power S Grover C Gentry AD Grant 《British journal of pharmacology》2013,168(3):761-772
Background and Purpose
The Ca2+-permeable cation channel TRPV4 is activated by mechanical disturbance of the cell membrane and is implicated in mechanical hyperalgesia. Nerve growth factor (NGF) is increased during inflammation and causes mechanical hyperalgesia. 4α-phorbol 12,13-didecanoate (4αPDD) has been described as a selective TRPV4 agonist. We investigated NGF-induced hyperalgesia in TRPV4 wild-type (+/+) and knockout (–/–) mice, and the increases in [Ca2+]i produced by 4αPDD in cultured mouse dorsal root ganglia neurons following exposure to NGF.Experimental Approach
Withdrawal thresholds to heat, von Frey hairs and pressure were measured in mice before and after systemic administration of NGF. Changes in intracellular Ca2+ concentration were measured by ratiometric imaging with Fura-2 in cultured DRG and trigeminal ganglia (TG) neurons during perfusion of TRPV4 agonists.Key Results
Administration of NGF caused a significant sensitization to heat and von Frey stimuli in TRPV4 +/+ and –/– mice, but only TRPV4 +/+ mice showed sensitization to noxious pressure. 4αPDD stimulated a dose-dependent increase in [Ca2+]i in neurons from +/+ and –/– mice, with the proportion of responding neurons and magnitude of increase unaffected by the genotype. In contrast, the selective TRPV4 agonist GSK1016790A failed to stimulate an increase in intracellular Ca2+ in cultured neurons. Responses to 4αPDD were unaffected by pretreatment with NGF.Conclusions and Implications
TRPV4 contributes to mechanosensation in vivo, but there is little evidence for functional TRPV4 in cultured DRG and TG neurons. We conclude that 4αPDD activates these neurons independently of TRPV4, so it is not appropriate to refer to 4αPDD as a selective TRPV4 agonist. 相似文献89.
90.
Helgason A Adolfsson J Dickman P Fredrikson M Steineck G 《Prostate cancer and prostatic diseases》1998,1(3):128-133
Based on traditional quality of life scales, it has been suggested that known side-effects of prostate cancer treatment do not influence the quality of life. The present authors have developed an alternative approach to quality of life assessment applying epidemiological methods. Using a self administered questionnaire, we investigated 431 prostate cancer patients and an age stratified sample of 435 randomly selected men. Patients reporting any level of distress due to waning sexual functions (66%) or urine or bowel symptoms (38%), reported a lower psychological well-being compared to patients not reporting these symptoms or patients not distressed by their symptoms. Our results stress that an intact sexual and urinary and bowel functions are important for the quality of life among elderly men with or without prostate cancer. 相似文献