全文获取类型
收费全文 | 155209篇 |
免费 | 45861篇 |
国内免费 | 1449篇 |
专业分类
耳鼻咽喉 | 2036篇 |
儿科学 | 5963篇 |
妇产科学 | 903篇 |
基础医学 | 30628篇 |
口腔科学 | 7160篇 |
临床医学 | 16234篇 |
内科学 | 31799篇 |
皮肤病学 | 5127篇 |
神经病学 | 22522篇 |
特种医学 | 6507篇 |
外国民族医学 | 4篇 |
外科学 | 18720篇 |
综合类 | 4519篇 |
现状与发展 | 2篇 |
一般理论 | 8篇 |
预防医学 | 9985篇 |
眼科学 | 1876篇 |
药学 | 18866篇 |
6篇 | |
中国医学 | 3303篇 |
肿瘤学 | 16351篇 |
出版年
2024年 | 107篇 |
2023年 | 1007篇 |
2022年 | 2056篇 |
2021年 | 3453篇 |
2020年 | 7330篇 |
2019年 | 13015篇 |
2018年 | 12404篇 |
2017年 | 13430篇 |
2016年 | 12258篇 |
2015年 | 12391篇 |
2014年 | 12859篇 |
2013年 | 13593篇 |
2012年 | 12179篇 |
2011年 | 12570篇 |
2010年 | 10909篇 |
2009年 | 7352篇 |
2008年 | 8013篇 |
2007年 | 6260篇 |
2006年 | 5898篇 |
2005年 | 5424篇 |
2004年 | 5242篇 |
2003年 | 4728篇 |
2002年 | 4215篇 |
2001年 | 3211篇 |
2000年 | 2151篇 |
1999年 | 909篇 |
1998年 | 718篇 |
1997年 | 651篇 |
1996年 | 570篇 |
1995年 | 524篇 |
1994年 | 453篇 |
1993年 | 437篇 |
1992年 | 429篇 |
1991年 | 385篇 |
1990年 | 322篇 |
1989年 | 295篇 |
1988年 | 240篇 |
1987年 | 244篇 |
1986年 | 231篇 |
1985年 | 490篇 |
1984年 | 597篇 |
1983年 | 392篇 |
1982年 | 447篇 |
1981年 | 403篇 |
1980年 | 346篇 |
1979年 | 321篇 |
1978年 | 275篇 |
1977年 | 185篇 |
1976年 | 167篇 |
1975年 | 132篇 |
排序方式: 共有10000条查询结果,搜索用时 19 毫秒
971.
Comparative genomic hybridization (CGH) analyses have detected gains of copy number on 13q, especially at 13q31-q32, in cell
lines and primary cases of various types of lymphoma. Since amplification of chromosomal DNA is one of the mechanisms that
can activate tumor-associated genes, and because 13q amplification had been reported in various other types of tumors as well,
we attempted to define by fluorescence in situ hybridization (FISH) a common region at 13q31-q32 in which to explore genes
that might be targets for the amplification events. Although the commonly amplified region we defined was relatively large
(approximately 4 Mb), only one true gene, GPC5, was found there. GPC5 was over-expressed in lymphoma cell lines that had shown amplification, in comparison with those that had not. Our findings
suggest that GPC5 is a likely target for amplification, and that over-expression of this gene may contribute to development and/or progression
of lymphomas and other tumors. 相似文献
972.
Tanaka Y Kato K Notohara K Nakatani Y Miyake T Ijiri R Nishimata S Ishida Y Kigasawa H Ohama Y Tsukayama C Kobayashi Y Horie H 《The Journal of pathology》2003,199(2):185-190
This study concerns the significance of aberrant (nuclear/cytoplasmic) expression of beta-catenin in pancreatoblastoma (PBL). On immunohistochemistry, all seven PBLs examined showed nuclear/cytoplasmic expression of beta-catenin, predominantly in the squamoid corpuscles (SCs). In areas with acinar/ductular differentiation, few tumour cells displayed nuclear/cytoplasmic expression of beta-catenin and more than half of the tumour cells showed membranous expression. Two out of five (40%) tumours examined showed missense mutations in codons 33 and 37 of exon 3 of the beta-catenin gene. No mutation of the adenomatous polyposis coli (APC) gene was detected in two of the remaining three tumours. Amplifiable DNA for APC analysis was not obtained from the one other tumour. Immunoreactivity for cyclin D1, one of the nuclear targets of beta-catenin, was found predominantly in the SCs of the seven tumours. In contrast, the Ki-67 labelling index was 2-4% (median 3%) in the SCs and 8-18% (median 12%) in the other areas, indicating a negative correlation with nuclear cyclin D1 reactivity. These results imply that in PBLs, nuclear/cytoplasmic accumulation of beta-catenin and overexpression of its target gene cyclin D1 are not associated with the induction of tumour cell proliferation. Nuclear/cytoplasmic accumulation of beta-catenin may be related to the morphogenesis of the SCs that are considered most characteristic for PBL. 相似文献
973.
Sasaki K Kato M Takahashi T Ochi S Ichinose Y Shiraki K Asano Y Iwanaga M Tsuji T 《Journal of medical virology》2003,70(2):329-335
This study was undertaken to determine whether the specific Th1- or Th2-cell response to varicella-zoster virus was induced predominantly by a mucosal adjuvant, cholera toxin, in mice. A commercially available live varicella vaccine (Oka strain) and cholera toxin or its B subunit were administered simultaneously via the nasal route. Delayed-type hypersensitivity to the Oka vaccine was induced, but the systemic neutralizing antibody response was low. The delayed-type hypersensitivity evoked after a single administration was relatively higher than that on administration three times. When spleen cells from mice immunized once with the vaccine and cholera toxin or its B subunit were restimulated with the live vaccine in vitro, there was greater thymidine uptake and production of interleukin- 2 (IL-2) than controls, but only a low level of IL-4 production. The production of IL-2 induced by the B subunit of cholera toxin was less than that by cholera toxin and a mutant of Escherichia coli enterotoxin on co-immunization with the vaccine in mice. Cholera toxin and its B subunit have been reported to induce predominantly a specific Th2-type T-cell response to various antigens. However, the Oka vaccine is an antigen that polarizes the activation of specific Th1/Th2-type T cells by cholera toxin or its B subunit to the Th1-type side. Cholera toxin and its B subunit are thus useful mucosal adjuvants for inducing cellular immunity to the Oka vaccine similar to Escherichia coli enterotoxin. 相似文献
974.
Talayev VY Zaichenko IY Babaykina ON Lomunova MA Talayeva EB Nikonova MF 《Clinical and experimental immunology》2005,141(3):440-448
The effects of dexamethasone phosphate and interleukin‐7 upon the proliferation of T‐cells and the production of interferon‐γ in the newborn's cord blood mononuclear cell cultures were studied. The capability of dexamethasone to enhance T‐cell proliferation induced by anti‐CD3 with interleukin‐7 in some newborn cord blood mononuclear cell cultures was identified. Dexamethasone suppressed production of interferon‐γ in 68‐h cell cultures stimulated with anti‐CD3 both in the presence of interleukin‐7 and without it. However, a 68‐h cultivation of newborn blood cells with dexamethasone, anti‐CD3 and interleukin‐7 resulted in the accumulation of T‐lymphocytes capable of producing interferon‐γ after restimulation. As a result of it the amount of interferon‐γ producing CD7+ T‐cells and the concentration of interferon‐γ in cultural supernatants were maximal in the cell cultures incubated with anti‐CD3, interleukin‐7 and dexamethasone during the first 68 h and subsequently restimulated with phorbol 12‐myristate 13‐acetate and ionomycin. The stimulation of neonatal or adult blood cells by dexamethasone, anti‐CD3 and interleukine‐7 also causes a decrease in the number of naïve T‐cells and central memory cells and an increase in the number of effector memory CD7+CD45RA+CD62L– cells in cultures. It is possible that these effects are caused by the influence of dexamethasone on IL‐7 receptor expression: it is known that IL‐7 receptor alpha‐chain gene is a glucocorticoid‐inducible gene. 相似文献
975.
Expression of human pim family genes is selectively up-regulated by cytokines promoting T helper type 1, but not T helper type 2, cell differentiation 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cytokines are the most important inducers of T helper (Th) cell differentiation. Interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) are responsible for human Th1-cell differentiation, while IL-4 is the critical cytokine promoting Th2-cell development. These two subsets of cells co-ordinate immunological responses to pathogens as well as autoimmune or allergic reactions. The pim family of proto-oncogenes encodes serine/threonine-specific kinases involved in cytokine-mediated signalling pathways in haematopoietic cells. Here we demonstrate that expression of pim-1 and pim-2 mRNAs is selectively up- or down-regulated in human cord-blood-derived CD4+ cells freshly induced to polarize towards Th1 or Th2 cells, respectively, whereas their expression is inhibited in both cell types by the immunosuppressive transforming growth factor beta (TGF-beta). Moreover, the Th1-specific cytokines IL-12 and IFN-alpha, but not the Th2-specific cytokine IL-4, transiently up-regulate pim-1 and pim-2 mRNA expression in human peripheral blood T cells and natural killer cells. In addition, the Pim-1 protein levels are strongly up-regulated by Th1-specific cytokines in all of these cell types. Taken together, our results suggest that pim genes and their protein products are involved in the early differentiation process of T helper cells. 相似文献
976.
In the event of smallpox bioterrorism, widespread vaccination may be required. Vaccinia immune globulin (VIG) has been used to treat complications from the smallpox vaccine. While the potency of VIG was defined by its ability to neutralize intracellular mature virus, a second form of vaccinia called the extracellular enveloped virus (EEV) is critical for virus spread in the host. The B5R-protein is one of many EEV-specific proteins. Immunoprecipitation and ELISA revealed that VIG recognizes the B5R-protein. An EEV plaque-reduction assay using a recombinant vaccinia that lacks the majority of the extracellular domain of B5R showed that the ability of VIG to neutralize EEV is principally directed at B5R. In addition, absorbing out the anti-B5R antibody present in VIG through the addition of recombinant B5R protein abrogated VIG's ability to significantly neutralize wild-type EEV. This work demonstrates the prominent role of B5R as a target of EEV-neutralizing activity of human antibodies. 相似文献
977.
Summary We have cloned the Cephalosporium acremonium pyr4 gene by cross-hybridization with the equivalent gene from Neurospora crassa, the closest relative from which this gene is available. The C. acremonium pyr4 gene complements an E. coli pyrF mutant lacking orotidine-5-phosphate decarboxylase (OMPdecase), and most probably does not contain introns. Maxicell analysis in E. coli shows that it encodes a 46 kDa polypeptide. The C. acremonium OMPdecase contains a highly conserved pentadecapeptide characteristic for this category of enzyme. Extensive sequence comparison suggests an important role of this region in enzymatic activity. 相似文献
978.
J.A. McLean J.R. Bacon K.P. Mathews J. Banas D. Capati N.K. Bayne 《The Journal of allergy and clinical immunology》1983,72(2):187-192
Preliminary experiments indicated that solutions of aspirin (ASA) in buffered saline, pH 7.35, did not significantly change nasal airways resistance (NAR) when 0.1 ml of solution containing 22.5 mg (or less) per deciliter was sprayed into each nostril. Subsequently it was shown that this quantity of ASA administered intranasally did not significantly change NAR responses 15 min later to intranasal administration of increasing concentrations of histamine, methacholine, or an irritant (NH3 gas). However, the same atopic subjects demonstrated significantly decreased responses to intranasal challenge with short ragweed extract (SRW) after intranasal ASA. In addition, prior oral administration of ASA, Na salicylate, and indomethacin significantly inhibited nasal challenge responses to SRW in sensitive subjects under controlled conditions. 相似文献
979.
Y Y Chua K Bremner N Lakdawalla J L Llobet H L Kokubu R P Orange C Collins-Williams 《The Journal of allergy and clinical immunology》1976,58(2):299-307
Sera of 86 patients clinically sensitive to foods were tested by passive sensitization of human and/or monkey lung (127 tests) and the radioallergosorbent test (RAST) (72 tests), using whole-food antigens; the results were compared with skin (prick) testing. Results of the prick test correlated with history in 76% of cases; lung sensitization correlated with history in 37% and with prick test in 57%; and RAST correlated with history in 54% and prick test in 72%. It is concluded that a very large percentage of adverse reactions to foods are IgE-mediated. The prick test is of use in diagnosis, particularly when combined with RAST; the lung sensitization test is technically impractical and not a reliable indicator. The best diagnostic method is careful history with food challenge and withdrawal and rechallenge; the latter is safe except in patients with a history of violent reaction. 相似文献
980.
A. V. Sergeev S. N. Bykovskaya L. M. Luchanskaya A. A. Ivanov M. O. Raushenbakh 《Bulletin of experimental biology and medicine》1977,84(2):1139-1142
The effect of different degrees of avitaminosis B6 in mice on the cytolytic activity of T lymphocytes, measured as the quantity of Na2Cr51O4 released from lysed target cells, was studied on a model of the primary immune response in a mixed lymphocyte culture in vitro. Keeping animals for 3 weeks on a diet without pyridoxine did not affect the ability of the lymphocytes to proliferate in vitro or their cytolytic activity. In animals receiving a diet without pyridoxine for 45 days the content of pyridoxal-5-phosphate in the spleen was 55% lower than in the control. Lymphocytes taken from these animals, when cultured in vitro, showed sharply weakened ability to incorporate [3H]thymidine into DNA in response to the alloantigen. The cytolytic activity of these lymphocytes also was reduced. The ability of different forms of pyridoxine to restore the functions of T lymphocytes, when disturbed by avitaminosis B6, was studied.Laboratory of Systemic Blood Diseases, Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Kraevskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 8, pp. 185–188, August, 1977. 相似文献