全文获取类型
收费全文 | 5364篇 |
免费 | 289篇 |
国内免费 | 132篇 |
专业分类
耳鼻咽喉 | 38篇 |
儿科学 | 153篇 |
妇产科学 | 54篇 |
基础医学 | 837篇 |
口腔科学 | 77篇 |
临床医学 | 300篇 |
内科学 | 744篇 |
皮肤病学 | 64篇 |
神经病学 | 264篇 |
特种医学 | 72篇 |
外科学 | 962篇 |
综合类 | 489篇 |
预防医学 | 394篇 |
眼科学 | 67篇 |
药学 | 733篇 |
2篇 | |
中国医学 | 181篇 |
肿瘤学 | 354篇 |
出版年
2023年 | 74篇 |
2022年 | 187篇 |
2021年 | 210篇 |
2020年 | 159篇 |
2019年 | 222篇 |
2018年 | 190篇 |
2017年 | 144篇 |
2016年 | 149篇 |
2015年 | 161篇 |
2014年 | 276篇 |
2013年 | 304篇 |
2012年 | 209篇 |
2011年 | 287篇 |
2010年 | 238篇 |
2009年 | 217篇 |
2008年 | 220篇 |
2007年 | 240篇 |
2006年 | 195篇 |
2005年 | 207篇 |
2004年 | 189篇 |
2003年 | 174篇 |
2002年 | 109篇 |
2001年 | 93篇 |
2000年 | 71篇 |
1999年 | 67篇 |
1998年 | 84篇 |
1997年 | 51篇 |
1996年 | 58篇 |
1995年 | 75篇 |
1994年 | 56篇 |
1993年 | 78篇 |
1992年 | 53篇 |
1991年 | 52篇 |
1990年 | 43篇 |
1989年 | 52篇 |
1988年 | 45篇 |
1987年 | 30篇 |
1986年 | 28篇 |
1985年 | 51篇 |
1984年 | 52篇 |
1983年 | 33篇 |
1982年 | 41篇 |
1981年 | 42篇 |
1980年 | 37篇 |
1979年 | 35篇 |
1978年 | 36篇 |
1977年 | 25篇 |
1976年 | 25篇 |
1975年 | 30篇 |
1973年 | 25篇 |
排序方式: 共有5785条查询结果,搜索用时 31 毫秒
41.
Ma HP Zhou ZH Liang YY Saxena S Warnock DG 《Pflügers Archiv : European journal of physiology》2004,449(1):96-105
Using whole-cell patch-clamp techniques we found that ATP activated an outwardly rectifying current in Daudi human B lymphoma cells under acidic conditions. The substitution of Cl– for gluconate– shifted the reversal potential, while Cl– channel blockers, 4,4-diisothiocyanostibene-2,2-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC), blocked the current, indicating that ATP induces this current by activating the outwardly rectifying chloride channel (ORCC). The effect of ATP on ORCC was mimicked by ADP, but not by other P2 receptor agonists such as ATPS (a poorly hydrolyzable analog of ATP), 2,3-O-benzoyl-4-benzoyl-ATP (BzATP), and UTP. The ATP-induced ORCC current was completely blocked by 100 M suramin (a P2 receptor antagonist), and was partially blocked by 100 M pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid tetrasodium (PPADS), which is another P2 receptor antagonist. Neither inactivation of G proteins nor elimination of extracellular Ca2+ affected the ATP-induced current, indicating that G protein-coupled P2Y receptors and Ca2+-permeable P2X receptors are not involved. Based on the pharmacological profile and the fact that acidic conditions are required for ATP to activate the ORCC, we suggest that acidic ATP activates the lymphocyte ORCC via a novel pathway, which is not associated with any previously described purinergic receptors. 相似文献
42.
Aidan P. McManus Barry A. Gusterson C. Ross Pinkerton Janet M. Shipley 《The Journal of pathology》1995,176(2):137-142
It is increasingly recognized that the identification of t(11;22)(q24;q12) is a useful aid in the accurate diagnosis of Ewing's sarcoma and related tumours. However, cytogenetic studies have a low success rate and adequate tumour is not always available. This study describes the use of fluorescence in situ hybridization (FISH) to detect translocations at 22q12, the site of the EWS gene involved in t(11;22)(q24;q12), on tumour touch imprints made from true cut core-needle biopsy and frozen tumour. Of the seven tumours analysed, five diagnosed as Ewing's sarcoma or primitive neuroectodermal tumour demonstrated chromosome translocation at 22q12. This is a rapid and reliable method to detect a diagnostically relevant chromosome translocation using minimal amounts of fresh or frozen tumour. 相似文献
43.
Objective To study the distribution and quantity of CD44VCD24- cells in breast cancer tissue and the cell lines,and as well as its correlation with the expression of various breast cancer markers and molecular subtyping of breast carcinoma.Methods The expression of CD44 / CD24,estrogen receptor,progesterone receptor,HER2,human estrogen-induced protein PS2,bcl-2 and nm23 in 60 cases of invasive ductal carcinoma of breast were studied by either single or double immunohistochemical staining.The co-expression of CD44 and CD24 in 3 breast cancer cell lines (MCF-7,MDA-MB-468,and MDA-MB- 231) was also examined.Results The quantity and distribution of CD44 + /CD24- cells varied greatly and no specific patterns were identified.The percentage of CD44 + /CD24- in breast cancer was 65%.The amount of CD44+/CD24- cells did not correlate with the age of patients,lymph node metastasis,tumor size,molecular subtypes and expression of various breast cancer markers in breast carcinoma.The proportion of CD44+/CD24- cells in MCF-7,MDA-MB-468,and MDA-MB-231 cell lines was < 1%,5% and > 80% ,respectively.Conclusions CD44+ /CD24- cells are demonstrated in certain breast cancer tissues and cell lines.However,there is no relationship obtained between the quantity or the distribution of these cells and the molecular subtyping or the clinicopathologic parameters in breast cancer. 相似文献
44.
Objective: We have evaluated the efficacy of the selective cyclo-oxygenase (COX)-2 inhibitor, rofecoxib, for the prevention of experimental colitis.Material and methods: To induce colitis BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Rofecoxib (2.5–10 mg/kg body weight, p.o.) was administered throughout the treatment period with DSS. Colitis was quantified by a clinical damage score, colon length, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1, prostaglandin (PG)E2 and PGD2 levels in colon mucosa and the immunohistochemical expression of COX-1 and –2 were also studied.Results: The COX-2 inhibitor ameliorated severe colitis, reduced the degree of inflammation through reduction of neutrophil infiltration and IL-1 levels. PGE2, and PGD2 synthesis were significantly reduced in DSS-treated groups. Indeed, treatment with rofecoxib diminished the lost of COX-1 caused by DSS in the crypt epithelium whereas expression of COX-2 remained unaffected.Conclusions: Rofecoxib is protective in acute DSS – induced colitis, probably by reducing neutrophil infiltration, inhibiting up-regulation of IL-1 and returning to normal COX-1 expression in the inflamed colonic mucosa.Received 19 April 2004; returned for revision 17 June 2004; accepted by I. Ahnfelt-Rønne 23 November 2004 相似文献
45.
目的: 研究胃良恶性病变组织中癌干细胞标记物CD24、CD44v6的表达并探讨其临床病理意义。方法: 49例胃癌、20例癌旁组织、36例淋巴结转移灶及80例不同类型胃良性病例(浅表性胃炎10例,萎缩性胃炎15例,胃溃疡20例,胃息肉20例,胃腺瘤15例)标本常规制作石蜡包埋切片,CD24和CD44v6染色方法为EnVision免疫组化法。结果: 胃癌病例CD24和CD44v6表达阳性率明显高于癌旁组织和不同类型胃良性病变(P<0.05或P<0.01),且阳性表达的良性病例胃黏膜上皮均呈中至重度不典型增生;转移灶CD24和CD44v6表达与相应原发灶呈现高度一致性(P>0.05);组织学分级Ⅱ级、无淋巴结转移及无远处器官转移胃癌病例CD24和CD44v6表达阳性率明显低于组织学分级Ⅲ或Ⅳ级、淋巴结转移及远处器官转移病例(P<0.05)。此外,浸润深度T1-T2及淋巴结N1站转移病例CD24表达阳性率明显低于浸润深度T3-T4和淋巴结N2、N3站转移病例(P<0.05)。结论: CD24和CD44v6表达可能是反映胃癌发生、进展、生物学行为和预后的重要癌干细胞标记物,检测胃良性病例CD24和CD44v6表达水平对预防和早期发现胃癌可能有一定的临床价值。 相似文献
46.
Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy 总被引:5,自引:0,他引:5
Mittag D Akkerdaas J Ballmer-Weber BK Vogel L Wensing M Becker WM Koppelman SJ Knulst AC Helbling A Hefle SL Van Ree R Vieths S 《The Journal of allergy and clinical immunology》2004,114(6):200-1417
BACKGROUND: We recently described patients with soybean allergy mainly mediated by cross-reactivity to birch pollen allergens. A majority of those patients were reported to have peanut allergy. OBJECTIVE: We sought to study the occurrence of peanut allergy in patients allergic to birch pollen and characterized the Bet v 1-homologous peanut allergen Ara h 8. METHODS: Recombinant Ara h 8 was cloned with degenerated primers and expressed in Escherichia coli. Nine Swiss and 11 Dutch patients with peanut and birch pollen allergy and a positive double-blind, placebo-controlled food challenge result to peanut were investigated for IgE reactivity to birch pollen and purified peanut allergens and cross-reactivity between birch and peanut. Ara h 8 stability against digestion and roasting was assessed by means of RAST inhibition. The IgE cross-linking potency of Ara h 8 was tested on the basis of basophil histamine release. RESULTS: During double-blind, placebo-controlled food challenge, all patients experienced symptoms in the oral cavity, progressing to more severe symptoms in 40% of patients. CAP-FEIA detected recombinant (r) Ara h 8-specific IgE in 85%. IgE binding to Ara h 8 was inhibited by Bet v 1 in peanut extract immunoblotting and in RAST inhibition. In EAST inhibition recombinant rAra h 8 inhibited IgE binding to peanut in 4 of 7 tested patient sera. Antipeanut response was dominated by Ara h 8 in 12 of 17 tested patients. Furthermore, our results demonstrate a low stability of Ara h 8 to roasting and no stability to gastric digestion. Basophil histamine release with rAra h 8 was more than 20% in 5 of 7 tested sera. CONCLUSIONS: Peanut allergy might be mediated in a subgroup of our patients by means of cross-reaction of Bet v 1 with the homologous peanut allergen Ara h 8. 相似文献
47.
Makoto Fujimura Takashi Kamakura Hirokazu Inoue Isamu Yamaguchi 《Current genetics》1994,25(5):418-422
We have previously shown that increased sensitivity to diethofencarb in the carbendazim(MBC)-resistant F914 strain of Neurospora crassa is caused by a single amino-acid change in -tubulin, 198Glu to Gly. Three diethofencarb-resistant mutants that are also resistant to MBC were isolated from strain F914. They contained single base-pair-substitution mutations in the -tubulin gene. The amino acid changes in -tubulin, Phe from 250Leu, Val from 165Ala, and Ala from 237Thr, were responsible for diethofencarb-resistance in the mutant strains FR511, FR513, and FR421, respectively. The amino acid at position 198 of -tubulin in these mutants was Gly, which is the same as in strain F914. -tubulin genes with 198Glu were constructed by site-directed mutagenesis. The altered -tubulin genes derived from FR511 and FR421 transformed the wild-type strain to resistance to MBC, indicating that 250Phe and 237Ala in -tubulin are responsible for resistance not only to diethofencarb but also to MBC. 相似文献
48.
Domnikova NP Degtyareva VV Nepomnyashchikh LM 《Bulletin of experimental biology and medicine》2004,138(6):593-597
Parameters of the erythroid, granulocytic, and megakaryocytic hemopoietic stems were compared in 87 patients with aggressive and indolent non-Hodgkins lymphomas before and 6 months after the start cytostatic therapy. Before chemotherapy anemia was detected in 46% patients with aggressive and 49% patients with indolent lymphomas. Hemoglobin content, peripheral blood erythrocyte count, and total count of erythroid cells in the bone marrow increased during chemotherapy in the indolent lymphoma group. Increased count of erythroid cells in the myelogram was due to decreased count of lymphoid cells in the bone marrow, which was associated with complete or partial remission. In aggressive lymphoma chemotherapy decreased the mean level of hemoglobin and mean erythrocyte count in the peripheral blood, but the total count of erythroid cells in the bone marrow increased; no relationship was detected between lymphocyte count in the bone marrow and erythropoiesis characteristics. Lymphocytosis >50% in the myelogram before chemotherapy was less frequent in this group in comparison with indolent non-Hodgkins lymphomas.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 12, pp. 668–673, December, 2004This revised version was published online in April 2005 with a corrected cover date. 相似文献
49.
Content of Autoantibodies to Bradykinin and β-Amyloid1-42 as a Criterion for Biochemical Differences between Alzheimer's Dementias 总被引:2,自引:0,他引:2
Myagkova MA Gavrilova SI Lermontova NN Kalyn YB Selezneva ND Zharikov GA Kolykhalov IV Abramenko TV Serkova TP Bachurin SO 《Bulletin of experimental biology and medicine》2003,136(1):49-52
We measured serum content of autoantibodies to -amyloid protein A1-42, its neurotoxic fragment A25-35, vasopressin, bradykinin, thrombin, antithrombin III, 2-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-A1-42 autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type. 相似文献
50.
Kadereit S Junge GR Kleen T Kozik MM Kaminski BA Daum-Woods K Fu P Tary-Lehmann M Laughlin MJ 《Journal of clinical immunology》2003,23(6):485-497
Regulation of nuclear factor of activated T cells-c2 (NFATc2) gene expression is not clearly defined. We previously reported reduced NFATc2 protein expression in cord blood T lymphocytes. Here we show that NFATc2 expression in T cells is dependent in part on the presence of IFN-gamma during primary stimulation, as blocking of IFN-gamma blunted NFATc2 protein and mRNA upregulation. Conversely, addition of exogenous IFN-gamma during stimulation resulted in increased expression of NFATc2 in cord blood T lymphocytes. This correlated with rescue of deficient IFN-gamma expression by cord blood T cells. Rescue of IFN-gamma expression in cord blood T cells was dependent on the presence of antigen-presenting cells, as addition of IFN-gamma during stimulation of purified cord blood T cells did not result in an increase of IFN-gamma expression, and depletion of monocytes ablated the rescue of IFN-gamma expression. Our results point to impaired function in the antigen-presenting cell population of cord blood, playing a role in the hyporesponsiveness of T cells. 相似文献