全文获取类型
收费全文 | 8044篇 |
免费 | 630篇 |
国内免费 | 54篇 |
专业分类
耳鼻咽喉 | 35篇 |
儿科学 | 175篇 |
妇产科学 | 165篇 |
基础医学 | 1369篇 |
口腔科学 | 191篇 |
临床医学 | 802篇 |
内科学 | 1797篇 |
皮肤病学 | 240篇 |
神经病学 | 937篇 |
特种医学 | 214篇 |
外科学 | 823篇 |
综合类 | 25篇 |
一般理论 | 5篇 |
预防医学 | 525篇 |
眼科学 | 113篇 |
药学 | 614篇 |
中国医学 | 10篇 |
肿瘤学 | 688篇 |
出版年
2024年 | 18篇 |
2023年 | 130篇 |
2022年 | 236篇 |
2021年 | 393篇 |
2020年 | 246篇 |
2019年 | 296篇 |
2018年 | 294篇 |
2017年 | 248篇 |
2016年 | 267篇 |
2015年 | 265篇 |
2014年 | 377篇 |
2013年 | 433篇 |
2012年 | 678篇 |
2011年 | 609篇 |
2010年 | 356篇 |
2009年 | 344篇 |
2008年 | 526篇 |
2007年 | 476篇 |
2006年 | 481篇 |
2005年 | 460篇 |
2004年 | 395篇 |
2003年 | 363篇 |
2002年 | 316篇 |
2001年 | 69篇 |
2000年 | 44篇 |
1999年 | 58篇 |
1998年 | 65篇 |
1997年 | 52篇 |
1996年 | 35篇 |
1995年 | 38篇 |
1994年 | 23篇 |
1993年 | 17篇 |
1992年 | 24篇 |
1991年 | 13篇 |
1990年 | 12篇 |
1989年 | 7篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1977年 | 4篇 |
1942年 | 1篇 |
1907年 | 2篇 |
1906年 | 3篇 |
1905年 | 3篇 |
1904年 | 2篇 |
1903年 | 4篇 |
排序方式: 共有8728条查询结果,搜索用时 15 毫秒
51.
Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells 总被引:7,自引:0,他引:7
Dvorak P Dvorakova D Koskova S Vodinska M Najvirtova M Krekac D Hampl A 《Stem cells (Dayton, Ohio)》2005,23(8):1200-1211
Although the detection of several components of the fibroblast growth factor (FGF) signaling pathway in human embryonic stem cells (hESCs) has been reported, the functionality of that pathway and effects on cell fate decisions are yet to be established. In this study we characterized expression of FGF-2, the prototypic member of the FGF family, and its receptors (FGFRs) in undifferentiated and differentiating hESCs; subsequently, we analyzed the effects of FGF-2 on hESCs, acting as both exogenous and endogenous factors. We have determined that undifferentiated hESCs are abundant in several molecular-mass isoforms of FGF-2 and that expression pattern of these isoforms remains unchanged under conditions that induce hESC differentiation. Significantly, FGF-2 is released by hESCs into the medium, suggesting an autocrine activity. Expression of FGFRs in undifferentiated hESCs follows a specific pattern, with FGFR1 being the most abundant species and other receptors showing lower expression in the following order: FGFR1 --> FGFR3 --> FGFR4 --> FGFR2. Initiation of differentiation is accompanied by profound changes in FGFR expression, particularly the upregulation of FGFR1. When hESCs are exposed to exogenous FGF-2, extracellular signal-regulated kinases are phosphorylated and thereby activated. However, the presence or absence of exogenous FGF-2 does not significantly affect the proliferation of hESCs. Instead, increased concentration of exogenous FGF-2 leads to reduced outgrowth of hESC colonies with time in culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether FGF-2 that is released by hESCs exerts its activities via autocrine pathways. Strikingly, the resultant inhibition of FGFR suppresses activation of downstream protein kinases and causes rapid cell differentiation, suggesting an involvement of autocrine FGF signals in the maintenance of proliferating hESCs in the undifferentiated state. In conclusion from our data, we propose that this endogenous FGF signaling pathway can be implicated in self-renewal or differentiation of hESCs. 相似文献
52.
Kuca K Cabal J Kassa J Jun D Hrabinová M 《Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové》2005,48(2):81-86
(1) The efficacy of the oxime HL?7 and currently used oximes (pralidoxime, obidoxime, HI-6) to reactivate acetylcholinesterase inhibited by various nerve agents (sarin, tabun, cyclosarin, VX) was tested by in vitro methods. (2) Both H oximes (HL?-7, HI-6) were found to be more efficacious reactivators of sarin and VX-inhibited acetylcholinesterase than pralidoxime and obidoxime. On the other hand, their potency to reactivate tabun-inhibited acetylcholinesterase is very low and does not reach the reactivating efficacy of obidoxime. In the case of cyclosarin, the oxime HI-6 was only found to be able to sufficiently reactivate cyclosarin-inhibited acetylcholinesterase in vitro. (3) Thus, the oxime HL?-7 does not seem to be more efficacious reactivator of nerve agent-inhibited acetylcholinesterase than HI-6 according to in vitro evaluation of their reactivation potency and, therefore, it is not more suitable to be introduced for antidotal treatment of nerve agent-exposed people than HI-6. 相似文献
53.
54.
55.
Martina C. Cornel Anthonie J. van Essen Leo P. ten Kate 《American journal of medical genetics. Part A》1992,42(3):387-392
After the birth of a child with a congenital anomaly, parents have many questions about cause, prognosis, and recurrence risk. An important means of transmitting such information is referral to a genetic clinic. We were interested in knowing what determines whether or not parents are referred for genetic counseling. Data from the local registration of congenital anomalies in the northeastern Netherlands (birth years 1981–1986; 1,217 children/fetuses) and data of the local genetic clinic were compared. The parents of 204 cases (16.8%) had been referred for genetic counseling. Of the couples referred, 76% were referred within one year after birth, usually by a pediatrician (48%). Parents of children with a single anomaly, recognized syndrome, or multiple anomalies not recognized as a syndrome were referred in 5%, 43%, and 26% of cases, respectively. Parents of liveborn children who died were referred in 38% of cases, parents of liveborn/still-alive and stillborn children in 13% and 22%, respectively. Previous affected sibs and absence of previous livebirths increased the likelihood of referral. 相似文献
56.
Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium 总被引:1,自引:0,他引:1
Martina Heer Christian Drummer Friedhelm Baisch Rupert Gerzer 《Pflügers Archiv : European journal of physiology》1993,425(5-6):390-394
The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects Ingested 2.8 mequiv sodium (kg body weight)–1 day–1 during the first phase, 5.6 mequiv (kg body weight)–1 day–1 during the second phase, and 8.4 mequiv (kg body weight)–1 day–1 during the third phase. The excretion of both sodium (P<0.002) and urodilatin (P<0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P<0.001). Serum aldosterone levels (P<0.01) as well as serum renin levels (P<0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P<0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance. 相似文献
57.
Florian Stehling Ralph Weber Arzu Özcelik Martina Bröcker Lothar Volbracht Hans-Christoph Diener Elmar Busch 《Neuroscience letters》2008
Thrombolysis is the only effective pharmaceutical therapy in acute ischemic stroke in humans but has a high risk of intracerebral hemorrhage. We aimed to establish an animal model to study changes of coagulation and fibrinolytic parameters during thromboembolic ischemic stroke and thrombolysis with recombinant tissue plasminogen activator (rt-PA). We used a thromboembolic stroke model in the rat. Animals were treated with rt-PA thrombolysis (n = 10) and compared with untreated (n = 10), sham operated (n = 10) and control animals (n = 20). Coagulation parameters (APTT, PT, TT, fibrinogen, AT III, TAT) and fibrinolytic parameters (t-PA antigen concentration, t-PA activity, PAI-1 concentration, PAI activity, plasminogen, antiplasmin) were measured at two time points (2.5 and 5 h after stroke induction) with a battery of commercially available test kits. We observed an (1) initiation of coagulation and inhibition of fibrinolysis by the operation procedure itself, (2) simultaneous activation of fibrinolysis and its inhibitors after stroke induction and (3) potent initiation of fibrinolysis and consumption of fibrinolysis inhibitors after rt-PA therapy of stroke. We established a model system to monitor coagulation and fibrinolysis during thrombolytic therapy of stroke in the rat. This model may be used to study the influence of these parameters on hemorrhagic stroke transformation and outcome in experimental stroke in future. 相似文献
58.
Wiesner M Zentz C Hammer MH Cobbold M Kern F Kolb HJ Hammerschmidt W Zeidler R Moosmann A 《European journal of immunology》2005,35(7):2110-2121
Efficient protocols to generate cytomegalovirus (CMV)-specific T cells are required for adoptive immunotherapy. Recombinant Epstein-Barr virus (EBV) vectors called mini-EBV can be used to establish permanent B cell lines in a single step, which present the CMV antigen pp65 in a constitutive manner. These B cell lines, coined pp65 mini-LCL, were successfully used to reactivate and expand CMV-specific cytotoxic T cells. Here we evaluate this pp65 mini-EBV system in closer detail, focusing on (1) the quantification of T cells with specific effector function and (2) the identification of CMV-specific CD4(+) helper T cells. The co-expansion of various functional CMV epitope specificities was demonstrated by IFN-gamma enzyme-linked immunospot assay (ELISPOT) assays and HLA-peptide tetramer staining. Single-cell cloning resulted in both CD4(+) and CD8(+) T cell clones, the majority of which was CMV specific. Thus, mini-LCL present the pp65 antigen on HLA class I and II, mobilizing both arms of the T cell response. Using a peptide library covering the pp65 sequence for further analysis of T cell clones, we identified new pp65 CD8(+) and CD4(+) T cell epitopes. 相似文献
59.
Ruiyi Ren Martina Nagel Emilios Tahinci Rudi Winklbauer Karen Symes 《Developmental dynamics》2006,235(4):1090-1099
Rho GTPases have been shown recently to be important for cell polarity and motility of the trunk mesoderm during gastrulation in Xenopus embryos. This work demonstrated that Rho and Rac have both distinct and overlapping roles in regulating cell shape, and the dynamic properties, polarity, and type of protrusive activity of these cells. Overexpression of activated or inhibitory versions of these GTPases also disrupts development of the head in Xenopus embryos. In this study, we have undertaken a detailed analysis of Rho and Rac function in migrating anterior mesendoderm cells. Scanning electron micrographs of these cells in situ revealed that their normal shingle arrangement is disrupted and both the cells and their lamellipodia are disoriented. Anterior mesendoderm explants plated on their natural blastocoel roof matrix, however, still migrated towards the animal pole, although the tendency to move in this direction is reduced compared to controls. Analysis of a number of parameters in time-lapse recordings of dissociated cells indicated that Rho and Rac also have both distinct and overlapping roles in the motility of the prospective head mesoderm; however, their effects differ to those previously seen in the trunk mesoderm. Both GTPases appear to modulate cell polarization, migration, and protrusive activity. Rho alone, however, regulates the retraction of the lagging edge of the cell. We propose that within the gastrulating Xenopus embryo, two types of mesoderm cells that undergo different motilities have distinct responses to Rho GTPases. 相似文献
60.
Alena Jiroutova Rastislav Slavkovsky Martina Cermakova Lenka Majdiakova Irena Hanovcova Radka Bolehovska Milena Hajzlerova Hana Radilova Ema Ruszova Jiri Kanta 《Experimental and toxicologic pathology》2007,58(4):263-273
Hepatic stellate cells (HSC) and liver myofibroblasts (MFB) are two cell populations most likely responsible for the synthesis of most connective tissue components in fibrotic liver. They differ in their origin and location, and possibly in patterns of gene expression. Normal and carbon tetrachloride-cirrhotic livers from rats were used to isolate HSC. Liver was perfused with pronase and collagenase solutions, followed by centrifugation of the cell suspension on a density gradient. HSC were quiescent 2 days after plating on plastic but they became activated after another 5 days in culture. When the culture was passaged 5 times, its character changed profoundly as HSC were replaced by MFB. Microarray analysis was used to determine gene expression in quiescent HSC, activated HSC and MFB. The expression of 49 genes coding for connective tissue proteins, proteoglycans, metalloproteinases and their inhibitors, growth factors and cellular markers was determined. The pattern of gene expression changed during HSC activation and there were distinct differences between HSC and MFB. Little difference between normal cells and cells isolated from cirrhotic liver was found. 相似文献