全文获取类型
收费全文 | 57705篇 |
免费 | 4048篇 |
国内免费 | 223篇 |
专业分类
耳鼻咽喉 | 684篇 |
儿科学 | 1474篇 |
妇产科学 | 1093篇 |
基础医学 | 7243篇 |
口腔科学 | 948篇 |
临床医学 | 5601篇 |
内科学 | 11816篇 |
皮肤病学 | 710篇 |
神经病学 | 5547篇 |
特种医学 | 1947篇 |
外国民族医学 | 4篇 |
外科学 | 9781篇 |
综合类 | 811篇 |
现状与发展 | 1篇 |
一般理论 | 69篇 |
预防医学 | 5111篇 |
眼科学 | 1177篇 |
药学 | 3548篇 |
中国医学 | 62篇 |
肿瘤学 | 4349篇 |
出版年
2023年 | 202篇 |
2022年 | 359篇 |
2021年 | 996篇 |
2020年 | 561篇 |
2019年 | 948篇 |
2018年 | 1156篇 |
2017年 | 799篇 |
2016年 | 893篇 |
2015年 | 994篇 |
2014年 | 1645篇 |
2013年 | 2437篇 |
2012年 | 3587篇 |
2011年 | 3886篇 |
2010年 | 2192篇 |
2009年 | 2020篇 |
2008年 | 3510篇 |
2007年 | 3689篇 |
2006年 | 3665篇 |
2005年 | 3749篇 |
2004年 | 3680篇 |
2003年 | 3360篇 |
2002年 | 3290篇 |
2001年 | 476篇 |
2000年 | 364篇 |
1999年 | 571篇 |
1998年 | 749篇 |
1997年 | 635篇 |
1996年 | 572篇 |
1995年 | 540篇 |
1994年 | 482篇 |
1993年 | 440篇 |
1992年 | 362篇 |
1991年 | 372篇 |
1990年 | 300篇 |
1989年 | 303篇 |
1988年 | 288篇 |
1987年 | 275篇 |
1986年 | 256篇 |
1985年 | 303篇 |
1984年 | 469篇 |
1983年 | 398篇 |
1982年 | 522篇 |
1981年 | 509篇 |
1980年 | 495篇 |
1979年 | 250篇 |
1978年 | 293篇 |
1977年 | 284篇 |
1976年 | 221篇 |
1975年 | 218篇 |
1974年 | 235篇 |
排序方式: 共有10000条查询结果,搜索用时 375 毫秒
991.
Charles P Hernandez MP Stankoff B Aigrot MS Colin C Rougon G Zalc B Lubetzki C 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(13):7585-7590
Many factors have been shown to promote myelination, but few have been shown to be inhibitory. Here, we show that polysialylated-neural cell adhesion molecule (PSA-NCAM) can negatively regulate myelin formation. During development, PSA-NCAM is first expressed on all growing fibers; then, axonal expression is down-regulated and myelin deposition occurs only on PSA-NCAM-negative axons. Similarly, in cocultures of oligodendrocytes and neurons, PSA-NCAM expression on axons is initially high, but decreases as myelination proceeds. Importantly, if expression of PSA-NCAM is prematurely decreased in cultures, by either antibody-mediated internalization or enzymatic removal of the PSA moieties with endoneuraminidase N (endo-N), myelination increases 4- to 5-fold. In the optic nerve, premature cleavage of PSA moieties by intravitreous injection of endo-N also induces a transient increase in the number of myelinated internodes, but does not interfere with the onset of myelination. Previously, we showed that axonal electrical activity strongly induced myelination, which could be prevented by tetrodotoxin (TTX), an action potential blocker. Interestingly, removal of PSA moieties does not reverse the inhibition of myelination by TTX. Together, this suggests that myelination is tightly controlled by both positive (electrical activity) and negative (PSA-NCAM expression) regulatory signals. 相似文献
992.
Freeman AJ Pan Y Harvey CE Post JJ Law MG White PA Rawlinson WD Lloyd AR Marinos G Ffrench RA 《Journal of hepatology》2003,38(3):349-356
BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection. 相似文献
993.
Phospholamban gene ablation improves calcium transients but not cardiac function in a heart failure model 总被引:6,自引:0,他引:6
Janczewski AM Zahid M Lemster BH Frye CS Gibson G Higuchi Y Kranias EG Feldman AM McTiernan CF 《Cardiovascular research》2004,62(3):468-480
Decreased amplitude and slower kinetics of cardiomyocyte intracellular calcium (Ca(i)(2+)) transients may underlie the diminished cardiac function observed in heart failure. These alterations occur in humans and animals with heart failure, including the TNF1.6 mouse model, in which heart failure arises from cardiac-specific overexpression of tumor necrosis factor alpha (TNF alpha). OBJECTIVE: Since ablation of phospholamban expression (PLBKO) removes inhibition of the sarcoplasmic reticulum (SR) Ca(2+) pump, enhances SR Ca(2+) uptake and increases contractility, we assessed whether ablation of phospholamban expression could improve cardiac function, limit remodeling, and improve survival in the TNF1.6 model of heart failure. METHODS: We bred PLBKO with TNF1.6 mice and characterized the progeny for survival, cardiac function (echocardiography), cardiac remodeling (hypertrophy, dilation, fibrosis), and Ca(2+)(i) transients and contractile function of isolated cardiomyocytes. RESULTS: PLB ablation did not improve survival, cardiac function, or limit cardiac chamber dilation and hypertrophy in TNF1.6 mice (TKO mice). However, contractile function and Ca(2+)(i) transients (amplitude and kinetics) of isolated TKO cardiomyocytes were markedly enhanced. This discordance between unimproved cardiac function, and enhanced Ca(2+)(i) cycling and cardiomyocyte contractile parameters may arise from a continued overexpression of collagen and decreased expression of gap junction proteins (connexin 43) in response to chronic TNF alpha stimulation. CONCLUSIONS: Enhancement of intrinsic cardiomyocyte Ca(2+)(i) cycling and contractile function may not be sufficient to overcome several parallel pathophysiologic processes present in the failing heart. 相似文献
994.
Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor 总被引:3,自引:0,他引:3
Magge SN Shyng SL MacMullen C Steinkrauss L Ganguly A Katz LE Stanley CA 《The Journal of clinical endocrinology and metabolism》2004,89(9):4450-4456
Familial leucine-sensitive hypoglycemia of infancy was described in 1956 as a condition in which symptomatic hypoglycemia was provoked by protein meals or the amino acid, leucine. The purpose of this study was to determine the genetic basis for hypoglycemia in a family diagnosed with leucine-sensitive hypoglycemia in 1960. Recently diagnosed family members showed a dominantly transmitted pattern of diazoxide-responsive hyperinsulinism (HI). However, they did not fit the characteristics of HI caused by glutamate dehydrogenase gene mutations, previously felt to explain leucine-sensitive hypoglycemia. Islet function was examined using acute insulin response (AIR) tests to calcium, leucine, glucose, and tolbutamide as well as oral protein tolerance tests. Five of five affected family members showed an abnormal positive calcium AIR, and two of five showed a positive leucine AIR. Protein-induced hypoglycemia was demonstrated in five of six affected subjects. Mutation analysis of four known HI genes (sulfonylurea receptor 1, Kir6.2, glutamate dehydrogenase, and glucokinase) in family members identified an R1353H missense mutation in exon 33 of SUR1. (86)Rb(+) efflux and electrophysiological studies of R1353H SUR1 coexpressed with wild-type Kir6.2 in COSm6 cells demonstrated partially impaired ATP-dependent potassium channel function. Leucine-sensitive hypoglycemia in this family was found to result from a dominantly expressed SUR1 mutation. 相似文献
995.
Cardiomyoplasty with skeletal myoblasts may benefit cardiac function after infarction. Recent reports indicate that adult stem cells can fuse with other cell types. Because myoblasts are "fusigenic" cells by nature, we hypothesized they might be particularly likely to fuse with cardiomyocytes. To test this, neonatal rat cardiomyocytes labeled with LacZ and green fluorescent protein (GFP) were cocultured with unlabeled C2C12 myoblasts. After 3 days, we observed a small population of skeletal myotubes that expressed LacZ and GFP, indicating cell fusion. To test whether such fusion occurred in vivo, LacZ-expressing C2C12 myoblasts were grafted into normal nude mouse hearts. At 2 weeks after grafting, cells at the graft-host interface expressed both LacZ and cardiac-specific myosin light chain 2v (MLC2v). To test more definitively whether fusion between skeletal and cardiac muscle could occur, we used a Cre/lox reporter system that activated LacZ only upon cell fusion. When neonatal cardiomyocytes from -myosin heavy chain promoter (-MHC)-Cre mice were cocultured with myoblasts from floxed-lacZ reporter mice, LacZ was activated in a subset of cells, indicating cell fusion occurred in vitro. Finally, we grafted the floxed-lacZ myoblasts into normal hearts of -MHC-Cre+ and -MHC-Cre- mice (n=5 each). Hearts analyzed at 4 days and 1 week after transplantation demonstrated activation of LacZ when the skeletal muscle cells were implanted into hearts of -MHC-Cre+ mice, but not after implantation into -MHC-Cre- mice. These data indicate that skeletal muscle cell grafting gives rise to a subpopulation of skeletal-cardiac hybrid cells with a currently unknown phenotype. The full text of this article is available online at http://circres.ahajournals.org. 相似文献
996.
Granulosa cell proliferation during luteinization and terminal differentiation has historically been assumed to decline rapidly after an ovulatory stimulus. In contrast, terminal differentiation in other cell types has recently been associated with a transient increase in proliferation, suggesting that this may occur in the ovarian follicle. The goal of the current study was to test the hypothesis that an ovulatory stimulus to rats results in additional granulosa cell proliferation before cell cycle arrest. Immature rats were given a single injection of pregnant mare serum gonadotropin (PMSG) followed by human chorionic gonadotropin (hCG) to initiate periovulatory events. The proportion of granulosa cells in S phase did not change until 12 h after hCG, although the majority of the post-hCG proliferation was localized to cumulus granulosa cells for up to 10 h after hCG. The expression of cyclin D2 mRNA did not decline until 12 h after hCG, although both cyclin-dependent kinase (Cdk)4 and Cdk6 mRNA increased at 6 h. Protein levels of cyclin D2 and Cdk4 did not change as a result of hCG, whereas cyclin E increased 6 h after hCG. Kinase activity of Cdk2 dropped markedly by 4 h after hCG, but a slight increase in activity was evident 6-8 h after hCG. These data suggest that cumulus granulosa cells continue to proliferate for up to 10 h after an ovulatory stimulus, possibly via cyclin E/Cdk2. It is concluded that proliferation is maintained in granulosa cells in the proximity of the oocyte during luteinization of the rat follicle. 相似文献
997.
Jean-François Rossi Bernard Klein Therese Commes Michel Jourdan Charles Janbon 《British journal of haematology》1988,68(2):207-212
T-cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL) have abnormal T4/T8 ratios and functions. Previously, we demonstrated that peripheral blood (PB) mononuclear cells from B-CLL patients secrete significant amounts of interleukin 2 (IL2) with an apparent dysregulation of accessory cells controlling this production. In this study, IL2 production was investigated in PB and in bone marrow (BM) from patients with previously untreated B-CLL, mostly in early stages of the disease, and compared to normal donors. A significant secretion was observed in both PB and BM from B-CLL patients after stimulation by phytohaemagglutinin (PHA), with lower amounts in patients with nodular involvement of BM, as compared to interstitial or diffuse involvements. To explore the role of accessory cells in controlling IL2 production, we added phorbol ester or indomethacin to the culture system or irradiated the cells before culture. Phorbol ester significantly increased the IL2 secretion in both the PB and the BM of B-CLL patients. The irradiation or the addition of indomethacin did not enhance the IL2 production in PB from B-CLL patients. However, IL2 secretion increased in the BM cells from B-CLL patients after addition of indomethacin or prior irradiation, in a similar way to that observed in PB and BM of normal controls, suggesting an apparent normal control of the IL2 production in BM from B-CLL patients. In normal controls, we demonstrated that IL2 secretion per T-cell from BM was 5.4-fold greater than that from normal PB, suggesting a very efficient role of accessory cells controlling IL2 production in normal BM. 相似文献
998.
The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: results of the Paris Prospective Study 总被引:6,自引:3,他引:6
M. A. Charles E. Eschwe`ge N. Thibult J.-R. Claude J.-M. Warnet G. E. Rosselin J. Girard B. Balkau 《Diabetologia》1997,40(9):1101-1106
Summary Although an increased plasma non-esterified fatty acid (NEFA) concentration has been shown to increase insulin resistance
(Randle cycle), decrease insulin secretion and increase hepatic gluconeogenesis, the effect of NEFA on the deterioration of
glucose tolerance has not been studied prospectively in Caucasian subjects. Therefore, we investigated whether plasma NEFA
may be regarded as predictors of deterioration of glucose tolerance in subjects with normal (NGT, n = 3671) or impaired (IGT, n = 418) glucose tolerance who were participants in the Paris Prospective study. The subjects were first examined between 1967
and 1972 and underwent two 75-g oral glucose tolerance tests 2 years apart with measurements of plasma glucose, insulin and
NEFA concentrations. Glucose tolerance deteriorated from NGT to IGT or non-insulin-dependent diabetes (NIDDM) in 177 subjects
and from IGT to NIDDM in 32 subjects. In multivariate analysis, high fasting plasma NEFA in NGT subjects and high 2-h plasma
NEFA and low 2-h plasma insulin concentrations in IGT subjects were significant independent predictors of deterioration along
with older age, high fasting and 2-h plasma glucose concentrations and high iliac to thigh ratio. When subjects were divided
by tertiles of plasma NEFA concentration at baseline, there was an increase in 2-h glucose concentration with increasing NEFA
in the subjects who did not deteriorate, but no effect of plasma NEFA in those who deteriorated. In subjects with IGT who
deteriorated compared with those who did not 2-h plasma insulin concentration was lower but there was no evidence that this
resulted from an effect of plasma NEFA. Our data suggest that a high plasma NEFA concentration is a risk marker for deterioration
of glucose tolerance independent of the insulin resistance or the insulin secretion defect that characterize subjects at risk
for NIDDM. [Diabetologia (1997) 40: 1101–1106]
Received: 11 March 1997 and in revised form: 20 May 1997 相似文献
999.
Pulmonary complications occur in 40% to 60% of recipients of bone marrow trans-plants, account for more than 90% of mortality, and develop during identifiable phases. Phase 1 (Days 1-30) includes pulmonary edema; diffuse alveolar hemorrhage; and various bacterial, fungal, and viral infections; Phase 2 (Days 31-100) usually requires a distinction between cytomegalovirus pneumonitis and idiopathic pneumonia syndrome; and Phase 3 (Day 100+) includes complications that are due to chronic graft-versus-host disease and associated bronchiolitis obliterans. The spectrum of pulmonary complications has been influenced by changes in transplantation technique, prophylactic treatment for infections, and the use of new chemotherapeutic agents that contribute to lung injury. Nonetheless, infections remain a leading cause of morbidity and mortality. The most serious complications result in respiratory failure, for which the prognosis has not improved significantly over the last 2 decades. In this article, we describe our algorithmic approach to the diagnosis and management of these complications. 相似文献
1000.
Increasing demand for population screening for the haemoglobinopathies gives rise to a requirement for high throughput systems, which allow for cost effective, rapid, sensitive and specific screening of clinically significant haemoglobins. We have developed a practical and efficient approach using tryptic digestion and electrospray triple quadrupole mass spectrometry-mass spectrometry (MSMS) in multiple reaction monitoring acquisition mode for the identification of the clinically important haemoglobin variants, S, C, DPunjab, OArab, and E. A total of 200 blood samples, comprising 52 haemoglobin AA, 57 AS (sickle cell trait), 44 AC (C trait), 16 SC (SC disease), 14 SS (sickle cell disease), 10 AE (E trait), 2 ADPunjab (DPunjab trait) and 1 each of AOArab (OArab trait), CC (C disease), DPunjabDPunjab (DPunjab disease), OArabOArab (OArab disease), and EE (E disease), have been analysed in parallel with existing phenotype and molecular methods. All haemoglobin variants were correctly identified by MSMS, with no false positives or false negatives. The system detects both heterozygotes and homozygotes and has potential applications in neonatal and antenatal screening. 相似文献