全文获取类型
收费全文 | 7499篇 |
免费 | 314篇 |
国内免费 | 33篇 |
专业分类
耳鼻咽喉 | 77篇 |
儿科学 | 159篇 |
妇产科学 | 132篇 |
基础医学 | 952篇 |
口腔科学 | 176篇 |
临床医学 | 480篇 |
内科学 | 1876篇 |
皮肤病学 | 153篇 |
神经病学 | 927篇 |
特种医学 | 201篇 |
外科学 | 1128篇 |
综合类 | 24篇 |
预防医学 | 194篇 |
眼科学 | 180篇 |
药学 | 419篇 |
中国医学 | 10篇 |
肿瘤学 | 758篇 |
出版年
2022年 | 66篇 |
2021年 | 127篇 |
2020年 | 80篇 |
2019年 | 116篇 |
2018年 | 144篇 |
2017年 | 98篇 |
2016年 | 99篇 |
2015年 | 123篇 |
2014年 | 184篇 |
2013年 | 223篇 |
2012年 | 341篇 |
2011年 | 353篇 |
2010年 | 205篇 |
2009年 | 160篇 |
2008年 | 291篇 |
2007年 | 341篇 |
2006年 | 298篇 |
2005年 | 351篇 |
2004年 | 287篇 |
2003年 | 317篇 |
2002年 | 289篇 |
2001年 | 216篇 |
2000年 | 252篇 |
1999年 | 197篇 |
1998年 | 82篇 |
1997年 | 69篇 |
1996年 | 55篇 |
1995年 | 71篇 |
1994年 | 71篇 |
1993年 | 49篇 |
1992年 | 179篇 |
1991年 | 175篇 |
1990年 | 153篇 |
1989年 | 174篇 |
1988年 | 153篇 |
1987年 | 127篇 |
1986年 | 117篇 |
1985年 | 131篇 |
1984年 | 104篇 |
1983年 | 87篇 |
1979年 | 79篇 |
1978年 | 53篇 |
1977年 | 57篇 |
1976年 | 49篇 |
1974年 | 51篇 |
1973年 | 58篇 |
1972年 | 53篇 |
1970年 | 55篇 |
1969年 | 56篇 |
1968年 | 45篇 |
排序方式: 共有7846条查询结果,搜索用时 15 毫秒
61.
We have investigated the potential of neurotropic microbes to invade the central nervous system (CNS) via the peripheral nervous system. Herpes simplex virus type 1 (HSV-1) strain KH6 and herpes simplex virus type 2 (HSV-2) strain 186 were found to infect chemosensory neurons in the vomeronasal organ (the pheromone detector) following intranasal inoculation of mice. HSV-1 strain KH6 infection was further transmitted to the accessory olfactory bulb (first relay), the medial amygdala (second relay), and the bed nucleus of the stria terminalis and the ventromedial hypothalamus (third relay). HSV-1 strain KH6 also targeted the olfactory and trigeminal systems. HSV-2 strain 186 predominantly attacked the brainstem including the trigeminal system. While both viruses did not induce apoptosis in infected chemosensory neurons, they did in infected brain tissue. These results suggest that neurotropic viruses can invade the brain by infecting vomeronasal chemosensory neurons and that the restrained induction of apoptosis in the infected neurons may facilitate viral transmission to the CNS. 相似文献
62.
Hiroki Kurahashi Kenzo Akagi Ikuo Yana Thomas Melot Olivier Delattre Gilles Thomas Shintaro Okada Shin-ichiro Takai Isamu Nishisho 《Journal of human genetics》1994,39(2):243-248
Summary Eight cosmid clones were regionally assigned to small subregions of chromosome 22 by hybridization with a total of 22 somatic cell hybrids. One cosmid was localized to the proximal part of 22q which contained the region commonly deleted in the DiGeorge syndrome. Seven cosmids showing restriction fragment length polymorphisms were localized to the telomeric region distal to the MB locus, which was reported to be frequently deleted in sporadic meningioma. These cosmids, when finely mapped and ordered, are considered useful for the identification of genetic alterations on this chromosome arm. 相似文献
63.
Toshitaka Nagao Thomas A Gaffey Hiromi Serizawa Isamu Sugano Yasuo Ishida Kazuto Yamazaki Ryoji Tokashiki Tomoyuki Yoshida Hiroshi Minato Paul A Kay Jean E Lewis 《Modern pathology》2003,16(12):1265-1272
Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated" carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma. 相似文献
64.
Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice 总被引:13,自引:0,他引:13
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-gamma), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha), resulting in macrophage activation and recruitment of circulating monocytes to initiate chronic granuloma formation. The cytokine that mediates macrophage activation is IFN-gamma, and, like IL-12, IL-18 was shown to activate Th1 cells and induce IFN-gamma production by these cells. In order to investigate the role of IL-18 in mycobacterial infection, IL-18-deficient mice were infected with Mycobacterium tuberculosis and Mycobacterium bovis BCG Pasteur, and their capacities to control bacterial growth, granuloma formation, cytokine secretion, and NO production were examined. These mice developed marked granulomatous, but not necrotic, lesions in their lungs and spleens. Compared with the levels in wild-type mice, the splenic IFN-gamma levels were low but the IL-12 levels were normal in IL-18-deficient mice. The reduced IFN-gamma production was not secondary to reduced induction of IL-12 production. The levels of NO production by peritoneal macrophages of IL-18-deficient and wild-type mice did not differ significantly. Granulomatous lesion development by IL-18-deficient mice was inhibited significantly by treatment with exogenous recombinant IL-18. Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-gamma expression. 相似文献
65.
Katabami K Mizuno H Sano R Saito Y Ogura M Itoh S Tsuji T 《Clinical & experimental metastasis》2005,22(7):539-548
66.
Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies 总被引:31,自引:0,他引:31
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Schlossmacher MG Frosch MP Gai WP Medina M Sharma N Forno L Ochiishi T Shimura H Sharon R Hattori N Langston JW Mizuno Y Hyman BT Selkoe DJ Kosik KS 《The American journal of pathology》2002,160(5):1655-1667
Mutations in alpha-synuclein (alpha S) and parkin cause heritable forms of Parkinson disease (PD). We hypothesized that neuronal parkin, a known E3 ubiquitin ligase, facilitates the formation of Lewy bodies (LBs), a pathological hallmark of PD. Here, we report that affinity-purified parkin antibodies labeled classical LBs in substantia nigra sections from four related human disorders: sporadic PD, inherited alphaS-linked PD, dementia with LBs (DLB), and LB-positive, parkin-linked PD. Anti-parkin antibodies also detected LBs in entorhinal and cingulate cortices from DLB brain and alphaS inclusions in sympathetic gangliocytes from sporadic PD. Double labeling with confocal microscopy of DLB midbrain sections revealed that approximately 90% of anti-alpha S-reactive LBs were also detected by a parkin antibody to amino acids 342 to 353. Accordingly, parkin proteins, including the 53-kd mature isoform, were present in affinity-isolated LBs from DLB cortex. Fluorescence resonance energy transfer and immunoelectron microscopy showed that alphaS and parkin co-localized within brainstem and cortical LBs. Biochemically, parkin appeared most enriched in cytosolic and postsynaptic fractions of adult rat brain, but also in purified, alpha S-rich presynaptic elements that additionally contained parkin's E2-binding partner, UbcH7. We conclude that parkin and UbcH7 are present with alphaS in subcellular compartments of normal brain and that parkin frequently co-localizes with alpha S aggregates in the characteristic LB inclusions of PD and DLB. These results suggest that functional parkin proteins may be required during LB formation. 相似文献
67.
Shoichi Fujita Eisei Shin Tsutomu Nakamura Hiroki Kurahashi Yasufumi Kaneda Kiyoji Tanaka Takesada Mori Shin-ichiro Takai Isamu Nishisho 《Journal of human genetics》1993,38(4):361-370
Summary Radiation-reduced hybrids for mapping of DNA markers in the pericentromeric region of chromosome 10 were developed. A Chinese hamster/human somatic cell hybrid (762-8A) carrying chromosomes 10 and Y as the only human material were exposed to 40,000 rads of irradiation and then rescued by fusion with non-irradiated recipient Chinese hamster cells (GM459). Southern hybridization analyses revealed that 10 of 128 HAT-resistant clones contained human chromosomal fragments corresponding to at least one marker locus betweenFNRB (10p-11.2) andRBP3 (10q11.2). These hybrids were then used to map microdissection clones previously isolated and roughly mapped to this chromosomal region by fluorescencein situ hybridization (FISH). Two of the six microclones studied could be mapped to the proximity of the D10-S102 locus. These radiation hybrids are useful for the construction of refined genetic maps of the pericentromeric region of chromosome 10. 相似文献
68.
K Mizuno K Satomura A Miyamoto K Arakawa T Shibuya T Arai A Kurita H Nakamura J A Ambrose 《The New England journal of medicine》1992,326(5):287-291
BACKGROUND. Disruption of an atherosclerotic plaque in a coronary artery followed by the formation of a thrombus is believed to be the cause of both unstable angina and acute myocardial infarction. Although thrombolytic therapy is efficacious in patients with acute myocardial infarction, for unknown reasons it is far less effective in patients with unstable angina. We postulated that there might be differences in the composition of the coronary-artery thrombi in unstable angina and acute myocardial infarction. METHODS. To investigate the appearance of coronary-artery thrombi, we performed percutaneous transluminal coronary angioscopy in 15 patients with unstable angina and 16 with acute myocardial infarction. Angioscopy was performed within 48 hours after an episode of pain at rest in the patients with unstable angina and within 8 hours of onset in those with acute myocardial infarction. RESULTS. Angioscopy revealed coronary thrombi in all but two patients (one in each group). Of the 29 patients with thrombi, those with unstable angina were frequently observed to have grayish-white thrombi (10 of 14, 71 percent), but none were seen in the 15 patients with acute myocardial infarction (P less than 0.01). By contrast, reddish thrombi were observed in all 15 patients with acute myocardial infarction who had thrombi, but in only 4 of the 14 patients with unstable angina and thrombi (P less than 0.01). As assessed by coronary angiography, occlusive thrombi occurred frequently in patients with acute myocardial infarction (13 of 16 patients) but were not seen in any of the 15 patients with unstable angina (P less than 0.01). CONCLUSIONS. Coronary-artery thrombi play an important part in the pathogenesis of unstable angina and acute myocardial infarction. However, the appearance of the thrombi is different in the two conditions, possibly reflecting differences in the composition of age of the thrombi or the presence or absence of blood flow in the artery. This difference may account for the contrasting results of thrombolytic therapy. 相似文献
69.
Shoa''a Al-Yousuf Akira Konishi Sakashi Nomura Noboru Mizuno 《Neuroscience letters》1992,140(2):189-191
Non-synaptic, exocytotic release of neurosecretory granules in cerebral ganglion neurons was observed electron microscopically in 3 species of the oligochaete annelids Aporrectodea caliginosa, Octolasion cyaneum and Lumbricus terrestris. In addition to the features indicating exocytotic release of neurosecretory granules into perineuronal space, possible features of neurosecretion into blood vessels were seen within the cerebral ganglion. Axon terminals in synaptic contact with perikaryal profiles of cerebral ganglion neurons were also found. 相似文献
70.
Assignment of a polymorphic locus of OS-4(D18S5) DNA segment to human chromosome region 18q21.3→qter