全文获取类型
收费全文 | 8063篇 |
免费 | 567篇 |
国内免费 | 465篇 |
专业分类
耳鼻咽喉 | 76篇 |
儿科学 | 88篇 |
妇产科学 | 168篇 |
基础医学 | 1219篇 |
口腔科学 | 120篇 |
临床医学 | 410篇 |
内科学 | 1661篇 |
皮肤病学 | 154篇 |
神经病学 | 769篇 |
特种医学 | 159篇 |
外科学 | 725篇 |
综合类 | 990篇 |
现状与发展 | 1篇 |
预防医学 | 250篇 |
眼科学 | 86篇 |
药学 | 1365篇 |
中国医学 | 153篇 |
肿瘤学 | 701篇 |
出版年
2024年 | 7篇 |
2023年 | 42篇 |
2022年 | 128篇 |
2021年 | 148篇 |
2020年 | 173篇 |
2019年 | 129篇 |
2018年 | 146篇 |
2017年 | 173篇 |
2016年 | 221篇 |
2015年 | 264篇 |
2014年 | 400篇 |
2013年 | 562篇 |
2012年 | 491篇 |
2011年 | 625篇 |
2010年 | 491篇 |
2009年 | 499篇 |
2008年 | 523篇 |
2007年 | 545篇 |
2006年 | 485篇 |
2005年 | 403篇 |
2004年 | 358篇 |
2003年 | 335篇 |
2002年 | 240篇 |
2001年 | 183篇 |
2000年 | 191篇 |
1999年 | 166篇 |
1998年 | 148篇 |
1997年 | 123篇 |
1996年 | 119篇 |
1995年 | 101篇 |
1994年 | 92篇 |
1993年 | 66篇 |
1992年 | 60篇 |
1991年 | 57篇 |
1990年 | 50篇 |
1989年 | 37篇 |
1988年 | 45篇 |
1987年 | 42篇 |
1986年 | 29篇 |
1985年 | 37篇 |
1984年 | 23篇 |
1983年 | 14篇 |
1982年 | 22篇 |
1981年 | 15篇 |
1980年 | 7篇 |
1979年 | 13篇 |
1978年 | 14篇 |
1977年 | 9篇 |
1974年 | 12篇 |
1973年 | 7篇 |
排序方式: 共有9095条查询结果,搜索用时 31 毫秒
51.
J. Škopková I. Albrecht J. H. Cort 《Pflügers Archiv : European journal of physiology》1973,343(2):123-132
Summary Rats anaesthetised with Inactin, body temp. maintained at 37°C, were infused with mannitol-saline until both urine flow rate and conductivity reached a balanced state. In separate experiments under analogous conditions cardiac output was measured by dye dilution and organ flow rates by86Rb distribution. Doses of oxytocin of 3 ng or less, injected at or just below the carotid bifurcation, caused a highly significant natriuresis with increased tubular rejection, but no measureable haemodynamic changes. The same oxytocin dose given into the internal or external carotid artery above the bifurcation caused neither haemodynamic changes nor natriuresis. Injection of vasopressin, angiotensin and -MSH at the sensitive site did not result in natriuresis in the same dosage range. Section of the sinus nerve significantly decreased the natriuretic response to oxytocin. It is suggested that the carotid body contains a specific oxytocin receptor capable of eliciting natriuresis in the rat. 相似文献
52.
抗hER合成肽单克隆抗体的制备与鉴定 总被引:1,自引:0,他引:1
用合成的人雌激素受体(hER)抗原决定簇多肽(氨基酸序列从151~165)与KLH的偶联物为抗原,免疫BALB/C小鼠,经鼠-鼠杂交,ELISA和免疫细胞化学法筛选,有限稀释克隆化,得到一株分泌抗hER合成肽的杂交瘤细胞株(2B12)。用ELISA法测定。该纯化抗体10ng/ml仍与抗原反应,其免疫球蛋白为IgG2a.k。与MCF-7乳腺癌细胞溶解蛋白的Westernblot分析,在分子量67kD 相似文献
53.
Settmacher B Rheinheimer C Hamacher H Ames RS Wise A Jenkinson L Bock D Schaefer M Köhl J Klos A 《European journal of immunology》2003,33(4):920-927
The anaphylatoxic peptide C3a is a pro-inflammatory mediator generated during complement activation, whose specific G protein coupled receptor is expressed on granulocytes, monocytes, mast cells, activated lymphocytes, and in the nervous tissue. We have generated RBL-2H3 cell clones stably expressing mutants of the human C3a-receptor (C3aR) with combined alanine (Ala) substitutions of ten C-terminal serine (Ser) or threonine (Thr) residues, which may represent putative phosphorylation sites to characterize their role in ligand-induced C3aR internalization and signaling. Ser475/479 and Thr480/481 as well as Ser449 seemed not to be involved in ligand-induced receptor internalization. Either directly or by a conformational change they even "inhibit" C3aR internalization. In contrast, mutants with Ala substitutions at Ser465/470 and Thr463/466 were poorly internalized, and Thr463 seemed to be the most important C-terminal Thr or Ser residue directly effecting receptor internalization. However, it is likely that other C3aR regions additionally participate in this negative feed-back mechanism since even mutants with multiple Ala substitutions still internalized to a limited degree. Interestingly, in a mutant with a single exchange of Ser449 to Ala, the signal transduction assessed by a Ca(2+) assay and [(35)S]GTP gamma S-binding on HEK cells transiently co-transfected with G-alpha 16 or G-alpha O, respectively, was severely impaired, indicating that this residue of C3aR is involved in G protein coupling. 相似文献
54.
Daniel F. Legler Marcel Loetscher Simon A. Jones Clemens A. Dahinden Michel Arock Bernhard Moser 《European journal of immunology》1996,26(4):753-758
The proteolytic cleavage product of complement component 3, (C3a), like C4a and C5a, is a potent anaphylatoxin and induces the production of inflammatory mediators in phagocytes. Notably, mast cells respond to C3a with the release of vasoactive substances, including histamine. We have examined the function and receptor binding of C3a in a human leukemic mast cell line, HMC-1. Similar to chemoattractant agonists in leukocytes, C3a induced rapid cytosolic free calcium concentration increases in HMC-1 cells. EGTA did not diminish this response, indicating that mobilizable Ca2+ was from intracellular stores. Receptors for C3a in HMC-1 cells couple in part to Bordetella pertussis toxin-sensitive G-proteins and, therefore, appear to belong to the family of serpentine receptors that require G-proteins for signal transduction. HMC-1 cells express two types of C3a receptors, C3aR1 and C3aR2, that were shown to bind 125I-C3a with high-(Kd1 = 2.1–4.8 nM) or low-affinity (Kd2 = 30–150 nM), and both receptors are expressed at high level: 3 × 105–6 × 105 C3aR1/cell and 5 × 105–2.3 × 106 C3aR2/cell. Results from cross-linking experiments with 125I-C3a fully agree with the presence of two different classes of C3a receptors in HMC-1 cells. Two membrane proteins with apparent molecular masses of 54–61 kDa (p57) and 86–107 kDa (p97) could be covalently modified with 125I-C3a, and this cross-linking was inhibited with an excess of unlabeled C3a. Many of the known agonists for leukocytes including 13 chemokines (IL-8, NAP-2, GROα, ENA-78, IP10, PF4, MCP-1, 2 and 3, RANTES, MIP-1α, MIP-1β and 1309), three neuropeptides (neuropeptide Y, somatostatin and calcitonin), as well as C5a, did not activate HMC-1 cells, indicating that C3a is one of a few protein ligands for which this cell line expresses specific receptors. The apparent selectivity for C3a and the abundant expression of C3a receptors make the HMC-1 cell line an excellent choice for the cloning of the receptor genes. 相似文献
55.
14只日本大耳白雄兔,7只为假手术组(SOG),7只为输精管结扎组(VG)。16个月后,检测前列腺睾酮受体和血清睾酮的变化。结果是VG和SOG胞液受体的kd值分别为10.21nM和3.42nM,最大结合容量分别为33.68fmol/mgpro.和10.42fmol/mg pro;胞核受体的kd值分别为9.36nM和4.81nM,最大结合容量分别为440.90fmol/mg DNA和203.66fmol/mg DNA。单点分析的结果是VG和SOG胞液受体浓度分别为26.13±5.64和8.40±1.66fmol/mg pro,VG明显高于SOG(P<0.01);胞核受体浓度分别为239.95±66.37和204.89±65.12fmol/mg DNA,两组比较无差异(P>0.05)。血清睾酮两组比较无统计学意义,并与胞液、胞核受体浓度无相关关系。 相似文献
56.
57.
《Human immunology》2022,83(2):130-133
The stimulation of AT1R (Angiotensin II Receptor Type 1) by Angiotensin II has, in addition to the effects on the renin-angiotensin system, also pro-inflammatory effects through stimulation of ADAM17 and subsequent production of INF-gamma and Interleukin-6. This pro-inflammatory action stimulate the cytokine storm that characterizes the most severe forms of SARS-CoV-2 infection. We studied the effect of AT1Rab on the AT1R on 74 subjects with SARS-CoV-2 infection with respiratory symptoms requiring hospitalization. We divided the patients into 2 groups: 34 with moderate and 40 with severe symptoms that required ICU admission. Hospitalized subjects showed a 50% reduction in the frequency of AT1Rab compared to healthy reference population. Of the ICU patients, 33/40 (82.5%) were AT1Rab negative and 16/33 of them (48.5%) died. All 7 patients positive for AT1Rab survived. These preliminary data seem to indicate a protective role played by AT1R autoantibodies on inflammatory activation in SARS-CoV-2 infection pathology. 相似文献
58.
Objective To investigate the effect of angiotensin (Ang) Ⅱ and its Janns-activated kinase-2 (JAK2) signal pathway in transdifferentiation of renal tubular cells under the challenge of acute ischemic reperfusion injury.Methods Models of acute ischemic reperfusion injury were established and the level of local Ang Ⅱ ,a key element of renin-angiotensin system (RAS),in kidney was measured using radioimmunity technique.The expression of α-smooth muscle actin (α-SMA),a phenotype of mesenchymal cells,was detected by RT-PCR and inununohistochemistry methods.Renal tubule cells ( NRK-52E) were cultured with various concentration of Ang Ⅱ ,followed by blocking of PD123319,Ang U receptor 2 antagonist,and AG490,an inhibitor of JAK2 signal pathway.Results Ang 0 of kidney tissue increased immediately after acute ischemic-reperfusion injury,in time dependent fashion.Expression of α-SMA in renal tubule cells was found at 48 hours after ischemic-reperfusion injury and in NRK-52E cells treated by high concentration of Ang Ⅱ and was dose and time dependent.The peak of α-SMA expression was seen after 30 minute treatment at the dose of 10-9'mol/L,which was interrupted by both of PD123319 and AG490.Conclusions Transdifferentiarion of renal tubular epithelial cells occurs under acute ischemic- reperfusion injury.Local renin-angiotensin system may play a role in the transdifferentiation of TEC through AT2 receptor and its JAK2 signal pathway. 相似文献
59.
目的:观察α-黑色素细胞刺激素(α-MSH)对脂多糖(LPS)诱导小鼠腹腔巨噬细胞CD14和TLR4 mRNA表达的影响,探讨α-MSH拮抗LPS的作用机制。方法:用半定量逆转录多聚酶链反应(RT-PCR)的方法检测LPS诱导体外培养的小鼠腹腔巨噬细胞CD14和TLR4 mRNA表达水平和给予α-MSH后对CD14和TLR4 mRNA表达的影响。结果:正常静息小鼠腹腔巨噬细胞只表达少量的CD14和TLR4 mRNA,给予LPS刺激后6 h,两者表达明显强于正常对照(P<0.01),并且其表达量随着LPS刺激时间的增加维持在高水平,24 h达到峰值,在48 h CD14 mRNA的表达降到正常水平,而TLR4 mRNA的表达仍然维持在高水平。在LPS刺激的同时给予α-MSH,CD14和TLR4 mRNA的表达则明显低于LPS组(P<0.05),而且α-MSH这种效应与其使用浓度有关,0.1 nmol/L α-MSH不影响LPS诱导的CD14和TLR4 mRNA的表达,而当α-MSH的浓度达到1、10、100 nmol/L则能显著影响CD14和TLR4 mRNA的表达(P<0.05),但各个浓度组之间的作用没有明显差别(P>0.05)。结论:α-MSH抗LPS的效应可能与其下调LPS信号转导通路关键受体CD14和TLR4 mRNA的表达有关,从而干扰LPS跨膜信号转导,阻碍巨噬细胞活化。 相似文献
60.
Iku Utsunomiya Kenji Tani Wanghua Gong Joost J. Oppenheim Ji Ming Wang 《European journal of immunology》1997,27(6):1406-1412
The C-C chemokine RANTES, a T lymphocyte chemoattractant, is considered an important mediator of inflammation, allergy, and host defense against HIV-1 infection. In this study, we investigated the modulation of binding of RANTES to T lymphocytes. Human peripheral blood CD3+ T cells, when freshly isolated from buffy-coat blood, expressed a considerable number of high-affinity binding sites for RANTES. These cells also showed significant chemotactic migration in response to RANTES in vitro. After 6–15 h incubation at 37°C, the binding of RANTES, but not of macrophage inflammatory protein-1α (MIP-1α) or of monocyte chemotactic protein-3 (MCP-3), consistently increased. Scatchard analyses indicated that the number of binding sites for RANTES increased about threefold by 15 h without any change in the affinity. The increase in RANTES binding was no longer detected by 24 h. This increase in the specific binding was mainly attributable to CD4+ T cells and was not associated with increased chemotactic activity of these cells in response to RANTES. Incubation with anti-CD3 antibody for 15 h markedly reduced the binding capability of T cells for RANTES and was associated with decreased chemotactic activity. On the other hand, when T cells were incubated with interleukin-2 (IL-2) for 1 week, the specific binding for all three C-C chemokines, RANTES, MIP-1α, and MCP-3 was markedly increased in comparison to cells cultured in the absence of IL-2. These results suggest that the expression of binding sites on T cells for RANTES is differentially modulated, indicating the existence of novel receptors for RANTES that do not bind MIP-1α. 相似文献