全文获取类型
收费全文 | 2265篇 |
免费 | 204篇 |
国内免费 | 80篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 34篇 |
妇产科学 | 16篇 |
基础医学 | 352篇 |
口腔科学 | 9篇 |
临床医学 | 182篇 |
内科学 | 361篇 |
皮肤病学 | 27篇 |
神经病学 | 240篇 |
特种医学 | 54篇 |
外国民族医学 | 2篇 |
外科学 | 139篇 |
综合类 | 282篇 |
现状与发展 | 1篇 |
预防医学 | 361篇 |
眼科学 | 7篇 |
药学 | 177篇 |
中国医学 | 26篇 |
肿瘤学 | 274篇 |
出版年
2024年 | 8篇 |
2023年 | 40篇 |
2022年 | 69篇 |
2021年 | 129篇 |
2020年 | 97篇 |
2019年 | 90篇 |
2018年 | 79篇 |
2017年 | 83篇 |
2016年 | 87篇 |
2015年 | 113篇 |
2014年 | 136篇 |
2013年 | 139篇 |
2012年 | 150篇 |
2011年 | 220篇 |
2010年 | 238篇 |
2009年 | 137篇 |
2008年 | 95篇 |
2007年 | 85篇 |
2006年 | 83篇 |
2005年 | 72篇 |
2004年 | 48篇 |
2003年 | 28篇 |
2002年 | 41篇 |
2001年 | 36篇 |
2000年 | 19篇 |
1999年 | 22篇 |
1998年 | 22篇 |
1997年 | 33篇 |
1996年 | 23篇 |
1995年 | 24篇 |
1994年 | 18篇 |
1993年 | 14篇 |
1992年 | 13篇 |
1991年 | 18篇 |
1990年 | 12篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
排序方式: 共有2549条查询结果,搜索用时 15 毫秒
21.
22.
23.
24.
- The subtype of α1-adrenoceptor mediating contractions to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery were investigated by use of antagonists which show selectivity between the cloned α1-adrenoceptor subtypes in binding studies.
- Cumulative concentration-contraction curves for phenylephrine were competitively antagonized in the rat thoracic aorta by prazosin (pA2 9.9), WB4101 (pA2 9.6), 5-methylurapidil (pA2 8.1), benoxathian (pA2 9.2) and indoramin (pA2 7.4). These compounds were also competitive antagonists in the mesenteric and pulmonary arteries (except for 5-methylurapidil in the pulmonary artery), (prazosin pA2 9.9 and 9.7; WB4101 pA2 9.8 and 9.6; 5-methylurapidil pA2 7.9 and pKB estimate 8.0; benoxathian pA2 8.8 and 9.3; indoramin pA2 7.2 and 7.5, respectively).
- RS 17053 was not a competitive antagonist in any blood vessel as Schild plot slopes were greater than unity. The pKB estimates for RS 17053 were 7.1 in aorta, 7.0 in the mesenteric artery and 7.7 in the pulmonary artery.
- The α1D-subtype selective antagonist BMY 7378 appeared to be non-competitive with shallow Schild plot slopes. The data were better fitted with two lines in all tissues, with Schild plot slopes that were no longer different from unity, except in the pulmonary artery. The higher affinity site for BMY 7378 in the aorta had a pA2 of 9.0, while it was 8.8 and 8.9 in the mesenteric and pulmonary arteries, respectively.
- MDL73005EF acted in a non-competitive manner in all three blood vessels, with shallow Schild plot slopes. The pKB estimates for MDL73005EF were 8.4 in aorta, 7.5 in the mesenteric artery and 8.0 in the pulmonary artery.
- In all three blood vessels the functionally determined antagonist affinity estimates correlated best with published pKi values for their displacement of [3H]-prazosin binding on membranes expressing cloned α1d-adrenoceptors compared with α1a- or α1b-adrenoceptors. The antagonist affinity estimates in the aorta, mesenteric and pulmonary arteries correlated highly with their previously published pA2 values in rat aorta (α1D) and less well with those for α1A- and α1B-adrenoceptors mediating contraction of the rat epididymal vas deferens and rat spleen, respectively.
- The results of this study suggest that the contraction to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery are mediated in part via the α1D-subtype of adrenoceptor. The data for both BMY 7378 and MDL73005EF in all three blood vessels are consistent with receptor heterogeneity. However, the identity of the second site is unclear.
25.
目的考察5-HT2C受体对孵育海马脑片释放分泌型淀粉样前体蛋白(sAPP)的调节。方法应用5-HT\,特异性5-HT2C受体激动剂M-110及其特异性拮抗剂L-107孵育海马脑薄片,及Western blot技术和特异性的针对sAPP氨基末端的单克隆抗体22C11检测释放到孵育液中的sAPP。结果5-HT及特异性5-HT2C受体激动剂M-110在一定的浓度范围内呈浓度依赖性地显著增加sAPP分泌;而特异性5-HT2C受体拮抗剂L-107在一定的浓度范围内则浓度依赖性地显著抑制sAPP分泌。结论5-HT通过激活5-HT2C受体调节孵育海马脑片分泌型淀粉样前体蛋白的释放。 相似文献
26.
目的查明河南省Ⅱ型汉坦病毒基因亚型的分布情况。方法在河南省汉坦病毒流行严重的地区,捕捉啮齿类动物,以免疫荧光法检测阳性标本,应用汉坦病毒型特异性引物以逆转录,聚合酶链反应方法对抗原检测阳性的鼠肺标本扩增M和S基因片段上的特异核苷酸序列并测序,将扩增片段的核苷酸序列与已知病毒序列进行比较,以明确基因亚型及其地理分布情况。结果褐家鼠、黄胸鼠以及小家鼠携带的病毒均为Ⅱ型汉坦病毒。序列分析发现河南省主要疫区宿主动物问流行的Ⅱ型汉坦病毒至少存在S1、S2和S3三个亚型,其中S1和S3为河南省汉坦病毒的优势流行基因亚型。结论河南省汉坦病毒的亚型较为复杂,地理分布较广。 相似文献
27.
Dopamine (DA) receptor subtype localization was investigated in rat cerebellar cortex using immunohistochemical techniques with antibodies raised against D1-D5 receptor protein. A faint D1 receptor protein immunoreactivity was developed in molecular and Purkinje neurons layers. D2 receptor protein immunoreactivity was found primarily in cerebellar white matter followed by molecular and granular layers and Purkinje neurons. Antibodies against D2S receptor protein were localized in molecular layer and to a lesser extent, in granular layer. A few Purkinje neurons displayed a faint D2S receptor protein immunoreactivity. D3 receptor protein immunoreactivity was observed primarily in molecular and in Purkinje neurons layers of lobules 9 and 10. A faint D3 receptor protein immunoreactivity was also localized in Purkinje neurons and to a lesser extent, in molecular and granular layers of cerebellar lobules 1-8. D4 receptor protein immunoreactivity was found in cerebellar white matter. A pale immunostaining was also visualized in molecular layer. D5 receptor protein immunoreactivity was localized primarily in molecular and Purkinje neurons layers and to a lesser extent, in granular layer and in white matter. The above results indicate that rat cerebellar cortex expresses the DA receptor subtypes so far identified. Purkinje neurons, which are the only efferent neurons of cerebellum, are richest in DA receptor protein immunoreactivity. This suggests that dopaminergic neurotransmission may modulate efferent inputs from cerebellum. The localization of the majority of D2 and D4 and of a faint D5 protein receptor immunoreactivity in cerebellar white matter suggests that these receptors may be presynaptic and transported axonally. 相似文献
28.
血凝素蛋白裂解位点对H5亚型禽流感病毒侵入细胞的影响 总被引:3,自引:0,他引:3
目的通过RT—PCR反应获得了H5N1亚型禽流感病毒完整的血凝素基因(HA)并克隆到真核表达载体pcDNA3上,通过转染293T细胞进行了瞬时表达验证。方法采用PCR定点突变技术,将其HA基因裂解位点的氨基酸组成由RKKR↓GLF突变为RSSR↓GLF,使其具有低致病性AIV的分子特征,并构建了表达突变后HA基因的真核表达载体pcDNA—Hm。将pcDNA—H5和pcDNA—Hm分别与MuLV假病毒构建体系的两种质粒pHTT60和pHIT111共转染转化了SV40大T抗原的人胚肾细胞293T后,收集转染细胞上清,通过Western—blot和细胞感染性实验来研究假病毒的特性。用缺乏囊膜蛋白和已经证实可以形成MuLV假病毒的水泡性口炎病毒糖蛋白G作为对照。结果转染后形成假病毒进行裂解后进行Westem—blot证明两种HA蛋白都能够整合到各自的假病毒颗粒表面,野生型的HA可以检测到三条带,分别与HA0、HA1和HA2大小相符,而突变后的HAm则仅能检测到一条带,与HA前体大小相符,说明其失去了裂解活性。通过感染293T、COS-7和NIH3T3三种不同的靶细胞后发现野生型的HA所形成的假病毒MuLV—H5具有感染性和泛嗜性,而突变后的HA所形成的假病毒则失去了感染性。结论可以得出HA蛋白裂解位点的氨基酸组成不仅对H5亚型禽流感病毒的致病性有影响,对禽流感病毒侵入细胞也具有至关重要的作用。 相似文献
29.
《Journal of neurogenetics》2013,27(4):134-139
Abstract: Voltage-gated sodium channels (VGSC) contribute to the initiation and propagation of action potentials within the nervous system. These channels are important targets for inhibition by several classes of drugs, including antiarrhythmics and local anesthetics. Structural and pharmacological studies have localized the binding of these drugs to a common site near the channel's intracellular pore region. Point mutations within this region disrupt local anesthetic inhibition of cardiac, CNS, and skeletal muscle VGSC subtypes. This study was designed to test whether a similar structural requirement for drug binding exists on the peripheral neuronal VGSC subtype; Nav1.7. In support of this hypothesis, an alanine substitution for phenylalanine at position 1737 (F1737A) in the pore lining S6 segment of domain IV in human Nav1.7 reduced both use- and state- dependent inhibition of the local anesthetics, lidocaine and tetracaine, by 8–21-fold. We also saw a 2–3-fold reduction in tonic inhibition with the F1737A mutant. The voltage dependence of both activation and inactivation were unaffected by the F1737A mutation, however, fast inactivation kinetics were impaired, such that a significant portion of inward current remained at the end of a 20-ms depolarization. These data suggest that F1737 forms a part of the high affinity binding of local anesthetics as well as mediating inactivation processes of neuronal Nav1.7 channels. 相似文献
30.
Tumour‐associated mast cells in classical Hodgkin's lymphoma: correlation with histological subtype,other tumour‐infiltrating inflammatory cell subsets and outcome
下载免费PDF全文
![点击此处可从《European journal of haematology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Patricia S. Nielsen Knud Bendix Rikke Riber‐Hansen Torben Steiniche Stephen Hamilton‐Dutoit Michael Clausen Francesco d'Amore 《European journal of haematology》2016,96(3):252-259
The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed–Sternberg cells within a heterogeneous background of non‐neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour‐infiltrating mast cells in cHL tissue microarrays and correlated this with clinico‐pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event‐free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications. 相似文献