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951.
目的 研究食管癌细胞Eca-109增殖、凋亡及COX-2表达与信号转导子和激活子3(STAT3)信号传导通路的关系,明确以JAK2/STAT3为靶向的信号转导在Eca-109细胞中的分子调控机制。方法 将JAK2抑制剂AG490作用于Eca-109细胞,用MTT法检测细胞增殖;流式细胞仪、DNA琼脂糖电泳法及透射电子显微镜检测细胞凋亡;Western blot法检测细胞中JAK2、p-JAK2、p-Stat3及COX-2的蛋白表达变化;RT-PCR 检测COX-2 mRNA的变化。结果 AG490呈时间、剂量依赖性的抑制Eca-109细胞增殖并诱导凋亡,抑制JAK2/STAT3通路蛋白的表达,呈浓度依赖性地下调p-JAK2及p-Stat3蛋白的表达(P <0.05),并下调COX-2 mRNA及蛋白的表达(P <0.05)。结论 JAK2/STAT3信号传导通路调控AG490对Eca-109细胞作用的细胞内信号传导机制,最终通过下调COX-2表达影响Eca-109细胞的增殖并诱导凋亡。 相似文献
952.
背景:研究表明外泌体具有促进骨再生的能力,但从胎牛血清中提取的外泌体是否可以促进骨形成仍存在争议。目的:观察胎牛血清外泌体对成骨细胞增殖能力的影响,从而为临床治疗骨破坏提供新思路。方法:通过超速离心法从胎牛血清中提取外泌体,采用透射电子显微镜和Western blot法验证外泌体是否提取成功;然后用10 mg/L胎牛血清外泌体干预成骨前体细胞MC3T3-E1,通过CCK-8实验检测外泌体对成骨细胞增殖能力的影响,Western blot检测外泌体对成骨细胞骨形态发生蛋白2和骨桥蛋白表达的影响。以不含外泌体的胎牛血清培养的MC3T3-E1细胞为对照组。结果与结论:①胎牛血清外泌体具有典型的脂质双层膜结构,大小在30-150 nm之间,外泌体表面标记因子CD81表达呈阳性,而微囊表面标记物CD40表达呈阴性;②外泌体组的增殖能力明显高于对照组,差异有显著性意义(P<0.05);外泌体组成骨标志性因子骨形态发生蛋白2和骨桥蛋白的表达水平明显高于对照组,差异有显著性意义(P<0.05);③结果表明,胎牛血清外泌体对成骨细胞的增殖起促进作用,可为临床治疗骨破坏提供新思路。 相似文献
953.
Daphné Lehalle Roberto Colombo Michael O'Grady Bénédicte Héron Nada Houcinat Paul Kuentz Sebastien Moutton Arthur Sorlin Julien Thevenon Julian Delanne Sebastien Gay Caroline Racine Aurore Garde Frédéric Tran Mau‐Them Christophe Philippe Antonio Vitobello Sophie Nambot Frédéric Huet Yannis Duffourd François Feillet Christel Thauvin‐Robinet Sandrine Marlin Laurence Faivre 《American journal of medical genetics. Part A》2019,179(9):1756-1763
Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDER) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management. 相似文献
954.
Among other characteristics, the steady-state current-voltage relationship of patch-clamped single atrial myocytes from guinea-pig hearts is defined by an outward current hump in the potential region –15 to +40mV. This hump was reversibly suppressed by Co2+ (3 mM) or nitrendipine (5 M) and enhanced by Bay K 8644 (5 M). The maintained outward current component suppressed by Co2+ extended between –15.2±1.9 mV and +39.5 ±1.7 mV (mean±SEM of 14 cells) and has an amplitude of 95.7±9.4 pA at +10 mV. In isochronal I-V curves, the hump was already visible at 400 ms with essentially the same amplitude as at 1500 ms. The Co2+ -sensitive outward current underlying the hump was poorly time-dependent during 1.5 s voltage pulses but slowly relaxed upon repolarization. Tail currents reversed near the K+ equilibrium potential under our experimental conditions. The current hump of the steady-state I-V curve was also abolished by caffeine (10 mM) or ryanodine (3 M), both drugs that interfere with sarcoplasmic reticulum function. Apamin (1 M) or quinine (100 M) but not TEA (5–50 mM) markedly reduced its amplitude. However, at similar concentrations as required to inhibit the hump, both apamin and quinine appeared to be poorly specific for Ca2+ -activated K+ currents in heart cells since they also inhibited the L-Type Ca2+ current. It is concluded that a long lasting Ca2+ -activated outward current, probably mainly carried by K+ ions but not sensitive to TEA, exists in atrial myocytes which is responsible for the current hump of the background I-V curve. 相似文献
955.
Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice. 下载免费PDF全文
F Wagner C Assemi C Lersch R Hart M Classen 《Clinical and experimental immunology》1990,82(2):344-349
Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation. 相似文献
956.
Kenji Naritomi Yoshinori Izumikawa Noriko Kinjo Chuken Miyagi Kiyotake Hirayama 《Journal of human genetics》1989,34(2):113-121
To identify the origin of a small inserted segment in ade novo 8p+ chromosome, an originally programmed computerized data-base for chromosomal aberration syndromes was utilized. The system selected 3q2 trisomy and 10q2 trisomy as candidates. As a result of a careful comparison of several high-resolution banding patterns among chromosomes 3, 10 and the inserted segment, her karyotype was disignated as: 46,XX,–8,+der(8), inv ins(8;3)(p21.1;q26.32q24)de novo. A small segment from 3q24 to 3q26.32 was trisomic, and invertedly inserted into the short arm of chromosome 8. This computerized database was considered to be useful for analyses of the smallde novo inserted chromosomal segment. 相似文献
957.
Liposomes could bind and fuse efficiently to human erythrocytes in the presence of HVJ when they contained gangliosides isolated from human erythrocytes. Sialosylparagloboside, which has a terminal sequence of NeuAcα2?3Ga1β1?4GlcNac, has a much higher receptor activity to the virus than GD1a, GD1b, GT1b, and GT1a, all of which contain the terminal sequence of NeuAcα2?3Galβ1?3GalNAc or NeuAcα2?8NeuAcα2?3Galβ1?3GalNAc. The activity of sialosylparagloboside is comparable to that of glycophorin, a major sialoglycoprotein of human erythrocytes, when compared on the basis of the required amount (as sialic acid) of compounds. The high affinity of sialosylparagloboside to the viral HANA protein is also suggested by the finding that it showed high inhibitory activity against HVJ-mediated binding of glycophorin liposomes to erythrocytes. Sialosylparagloboside was also highly susceptible to the viral sialidase, the other biological function of HANA protein. 相似文献
958.
Akagi M Inui K Nakajima S Shima M Nishigaki T Muramatsu T Kokubu C Tsukamoto H Sakai N Okada S 《Journal of human genetics》2000,45(1):60-62
Fanconi-Bickel syndrome (FBS), or glycogen storage disease type XI, is a rare autosomal recessive disorder characterized
by hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Recently, this
disease was elucidated to link mutations in the glucose transporter 2 (GLUT2) gene. Only three mutations in three FBS families have been reported. Therefore, it is important to elucidate mutations in
the GLUT2 gene in FBS by answering the question of whether the syndrome is a single gene disease. In this report, we describe two patients
in two unrelated families clinically diagnosed with FBS. No mutation in the entire protein coding region of the GLUT2 gene was detected in patient 1, which suggested that no mutation existed in the GLUT 2 gene, or that some mutations had affected the expression of the GLUT 2 gene. In patient 2, a novel homozygous nonsense mutation (W420X, Trp at codon 420 to stop codon) was detected. These results
support the correlation between GLTU2 gene mutation and FBS syndrome. However, many patients must be analyzed to determine whether other genes are involved in
FBS.
Received: July 16, 1999 / Accepted: September 3, 1999 相似文献
959.
Effects of ruthenium red on membrane ionic currents in urinary bladder smooth muscle cells of the guinea-pig 总被引:2,自引:0,他引:2
Masaru Hirano Y. Imaizumi Katsuhiko Muraki A. Yamada Minoru Watanabe 《Pflügers Archiv : European journal of physiology》1998,435(5):645-653
Three major ionic currents, Ca2+-dependent K+ current (I
K-Ca), delayed rectifier type K+ current (I
kd) and Ca2+ current (I
Ca), were activated by depolarization under whole-cell clamp in single smooth muscle cells isolated from guinea-pig urinary
bladder. Externally applied ruthenium red (RuR) reduced the amplitude of I
K-Ca and I
Ca at 0 mV (IC50 values were 4.2 and 5.6 μM, respectively), but did not affect I
Kd. Spontaneous transient outward currents (STOCs) and caffeine-induced outward currents (I
caf) at –30 mV were reduced by external 10 μM RuR. When 10 μM RuR was added to the pipette solution, I
K-Ca during depolarization, STOCs and I
caf significantly decreased with time. RuR did not change the unitary current amplitude of the large-conductance Ca2+-dependent K+ (BK) channels, but reduced the open probability of the channel under excised patch-clamp recording mode. RuR reduced the
channel activity more effectively from the cytosolic face than from the other. This inhibition decreased when the cytosolic
Ca2+ concentration was increased. These results indicate that RuR blocks BK and Ca2+ channels in urinary bladder smooth muscle cells. The decrease in I
K-Ca, STOCs and I
caf by RuR is attributable to the direct inhibition of BK channel activity, probably in addition to the inhibition of Ca2+ release from storage sites. The direct inhibition of BK channel activity by RuR may be related to the interaction of RuR
with the Ca2+-binding sites of the channel protein.
Received: 15 October 1997 / Received after revision and accepted: 25 November 1997 相似文献
960.
Anupama Kohli MD Stephen P. Baker MCS MPH Nilima A. Patwardhan MD Ashraf Khan MD MRCPATH 《Endocrine pathology》1998,9(2):117-123
Previous studies have established that thyroid follicular neoplasms of higher malignant potential show a high p53 and low
bc1-2 expression. This however has not been well studied in Oncocytic (Hürthle cell) neoplasms, the management of which remains
controversial. We therefore studied the expression of p53 and bc1-2 in 18 Hürthle cell adenomas (HCA) and 8 Hürthle cell carcinomas
(HCC) and compared them with their benign and malignant counterparts, respectively, including 16 follicular adenomas (FA)
and 68 papillary carcinomas (PC). All 16 FA were bc1-2 positive, 4 were 2+, and 12 were 3+. On the other hand, 14/18 (78%)
HCA showed bc1-2 expression, 5 were 1+, 6 were 2+, and only 3 were 3_. Similarly, HCC showed a weaker bc1-2 staining pattern
compared to PC. Only 1 FA showed grade 1, p53 staining, the remaining 15 were negative, and 15/18 HCA showed p53 expression
of varying grades. This difference in p53 staining was statistically significant (p=0.005). A significant p53 overexpression was also seen in HCC compared to PC (p=0.005). In conclusion, there appears to be an inverse relationship between p53 and bc1-2 expression in thyroid follicular
neoplasms. A higher expression of p53 and lower levels bc1-2 in Hürthle cell neoplasms may have biological and clinical implications.
This may support a more aggressive surgical treatment for HCA compared to FA. 相似文献