全文获取类型
收费全文 | 13192篇 |
免费 | 697篇 |
国内免费 | 95篇 |
专业分类
耳鼻咽喉 | 88篇 |
儿科学 | 225篇 |
妇产科学 | 123篇 |
基础医学 | 2139篇 |
口腔科学 | 97篇 |
临床医学 | 1355篇 |
内科学 | 2926篇 |
皮肤病学 | 356篇 |
神经病学 | 1293篇 |
特种医学 | 529篇 |
外科学 | 2016篇 |
综合类 | 48篇 |
一般理论 | 2篇 |
预防医学 | 652篇 |
眼科学 | 215篇 |
药学 | 917篇 |
中国医学 | 40篇 |
肿瘤学 | 963篇 |
出版年
2023年 | 62篇 |
2022年 | 83篇 |
2021年 | 255篇 |
2020年 | 151篇 |
2019年 | 223篇 |
2018年 | 316篇 |
2017年 | 201篇 |
2016年 | 236篇 |
2015年 | 268篇 |
2014年 | 371篇 |
2013年 | 510篇 |
2012年 | 902篇 |
2011年 | 1020篇 |
2010年 | 601篇 |
2009年 | 534篇 |
2008年 | 869篇 |
2007年 | 1007篇 |
2006年 | 905篇 |
2005年 | 945篇 |
2004年 | 875篇 |
2003年 | 858篇 |
2002年 | 837篇 |
2001年 | 135篇 |
2000年 | 102篇 |
1999年 | 143篇 |
1998年 | 211篇 |
1997年 | 163篇 |
1996年 | 161篇 |
1995年 | 109篇 |
1994年 | 109篇 |
1993年 | 108篇 |
1992年 | 93篇 |
1991年 | 57篇 |
1990年 | 45篇 |
1989年 | 59篇 |
1988年 | 44篇 |
1987年 | 39篇 |
1986年 | 41篇 |
1985年 | 27篇 |
1984年 | 44篇 |
1983年 | 38篇 |
1982年 | 41篇 |
1981年 | 30篇 |
1980年 | 34篇 |
1979年 | 23篇 |
1978年 | 19篇 |
1977年 | 16篇 |
1976年 | 10篇 |
1975年 | 8篇 |
1974年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
71.
Antoine Alam Jacqueline Lul H l ne Coppin Nathalie Lambert Bernard Mazi res Claude De Pr val Alain Cantagrel 《Human immunology》1995,42(4):331-339
In order to look for a site-specific T-cell response in RA SM, PCR analyses using oligonucleotide primers specific for 24 TCRBV (Vβ) families were performed to compare the respective usage of each TCRBV gene by T cells present in PB and SM of 13 patients with RA. In four patients, SM cells from two or three sites of inflammation were subjected to analysis. In one patient, synovial tissue was studied at two different phases of the disease, resulting in a total number of 19 samples of SM cells, which were compared with paired samples of PB cells. The results showed that whereas all 24 TCRBV gene families could be detected in both PB and SM cells, there was some skewing of increased or decreased usage frequencies of particular TCR Vβ genes among SM cells. Three TCRBV families were often overexpressed in SM: Vβ3, Vβl7, and Vβ22. Moreover, Vβ4 was often decreased in SM (7 out of 13). This decrease was statistically significant in the RA population studied. SM from different joints of a given patient showed similar variations of T-cell repertoire compared to PB, even 6 months later in the course of the disease. These results demonstrate a biased TCRBV gene utilization in RA SM. This bias appears to be similar in different joints and at different times in the course of the disease. No correlation was found between the bias of TCR repertoire in SM and the HLA typing of these patients. 相似文献
72.
Properties of simian virus 40 mutants lacking the Asp4-Glu-Asp stretch at the carboxyl-terminus of large T antigen 总被引:1,自引:0,他引:1
The biological activity carried by the carboxy-terminal domain of SV40 large T antigen has been investigated by isolating mutants deleted for a stretch of six acidic residues which by analogy with polyoma middle T antigen might be essential for the activity of the protein. We have constructed an "in-phase" deletion of 37 residues that includes the complete acid residues cluster. In order to parallel the polyoma hr-t mutants genotype, the deletion was introduced in virus strains either competent or defective for the small t antigen. We conclude from these experiments that the deletion of this unusual sequence does not affect per se any of the known biological properties of the virus. 相似文献
73.
Liliane Schanden Alina Ferster Franoise Mascart-Lemone Alain Crusiaux Catherine Grard Arnaud Marchant Myriam Lybin Thierry Velu Eric Sariban Michel Goldman 《European journal of immunology》1993,23(1):56-60
We characterized the defects of CD4+ cells in a 17-month-old girl suffering from combined immunodeficiency with hypereosinophilia (Omenn's syndrome). Because the vast majority of peripheral blood CD4+ cells expressed the CD45R0 isoform, we purified circulating CD4+ CD45R0+ cells from the patient and healthy individuals in order to compare their production of cytokines. The patient's CD4+ CD45R0+ cells spontaneously produced high levels of interleukin-5 (IL-5) in vitro (1600 pg/ml after 24 h of culture) and this was associated with the presence of IL-5 in serum (323 pg/ml). After stimulation with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187, they produced higher levels of IL-4 (306 vs. 55 ± 4 pg/ml) and IL-5 (2900 vs. 213 ± 72 pg/ml) and lower levels of IL-2 (17 vs. 63 ± 17 IU/ml) and interferon-γ (IFN-γ) (16 vs. 299 ± 70 IU/ml) than controls CD4+ CD45R0+ cells. This T helper type 2 (Th2) pattern was confirmed by the detection using reverse polymerase chain reaction of IL-4, IL-5 and IL-10 mRNA within peripheral blood mononuclear cells. During a therapeutic trial with human IFN-γ (40 μg/day) which ameliorated the clinical status of the patient, we observed a down-regulation of the in vivo expression of IL-5 and IL-10, a normalization of the eosinophil count and an improvement of the Tcell response to phytohemagglutinin. This observation indicates for the first time that Th2-like cells might be involved in certain forms of congenital immunodeficiency and that IFN-γ might down-regulate their activities in vivo. 相似文献
74.
Salamon R Marimoutou C Ekra D Minga A Nerrienet E Huët C Gourvellec G Bonard D Coulibaly I Combe P Dabis F Bondurand A Montagnier L 《Journal of acquired immune deficiency syndromes (1999)》2002,29(2):149-157
OBJECTIVE: To describe the clinical and biologic evolution of HIV-1 infection in Africa. METHODS: One hundred four HIV-1-infected individuals were identified prospectively from regular blood donors in Abidjan, C?te d'Ivoire. The date of seroconversion was estimated from results of sequential serologic tests. Biologic and clinical follow-up was performed every 6 months, starting as early as possible after seroconversion. Case management followed national guidelines. RESULTS: The median interval between estimated seroconversion and study inclusion was 9.7 months, and the median window of seroconversion was 2.8 months. At baseline, all but two patients were asymptomatic; the median CD4 + cell count was 527/mm 3 (interquartile range [IR], 395-684), and the median plasma HIV RNA level was 4.6 log 10 copies/ml (IR, 3.8-4.9). The median follow-up was 23.9 months, and 95% of the patients received primary prophylaxis with co-trimoxazole for opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3 developed tuberculosis, and 17 had a Centers for Disease Control and Prevention category B-defining event. The 3-year AIDS-free and symptom-free probabilities were 96.7% (95% confidence interval [CI], 87.0-99.2] and 79.3% (95% CI, 67.5-87.2), respectively. During the first 3 years of follow-up, we observed that the median plasma viral load stabilized at >4 log 10 copies/ml and that the median CD4 + cell count declined by 20 to 25/mm 3 per year. CONCLUSION: These African seroconverters were moderately immunosuppressed. The median HIV RNA level was high and varied very little during the first 3 years, and there were few clinical events. 相似文献
75.
Identification of B- and T-Cell Epitopes of BB, a Carrier Protein Derived from the G Protein of Streptococcus Strain G148
下载免费PDF全文
![点击此处可从《Clinical and Vaccine Immunology : CVI》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Liliane Goetsch Jean Francois Haeuw Thierry Champion Christine Lacheny Thien NGuyen Alain Beck Nathalie Corvaia 《Clinical and Vaccine Immunology : CVI》2003,10(1):125-132
Most conventional vaccines consist of killed organisms or purified antigenic proteins. Such molecules are generally poorly immunogenic and need to be coupled to carrier proteins. We have identified a new carrier molecule, BB, derived from the G protein of Streptococcus strain G148. We show that BB is able to induce strong antibody responses when conjugated to peptides or polysaccharides. In order to localize T and B cell epitopes in BB and match them with the albumin-binding region of the molecule, we immunized mice with BB, performed B and T pepscan analyses, and compared the results with pepscan done with sera and cells from humans. Our results indicate that BB has two distinct T helper epitopes, seven linear B-cell epitopes, and one conformational B-cell epitope in BALB/c mice. Four linear B-cell epitopes were identified from human sera, three of which overlapped mouse B-cell epitopes. Finally, three human T-cell epitopes were detected on the BB protein. One of these T-cell epitopes is common to BALB/c mice and humans and was localized in the region that contains the albumin-binding site. These data are of interest for the optimization of new carrier molecules derived from BB. 相似文献
76.
Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction 总被引:12,自引:0,他引:12
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)
Gabison EE Mourah S Steinfels E Yan L Hoang-Xuan T Watsky MA De Wever B Calvo F Mauviel A Menashi S 《The American journal of pathology》2005,166(1):209-219
Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally identified on the tumor cell surface as an inducer of matrix metalloproteinase (MMP) production in neighboring fibroblasts. Here we demonstrate a role for EMMPRIN in MMP induction during corneal wound healing. MMP and EMMPRIN expression was analyzed in normal and ulcerated human corneas, as well as in corneal epithelial and stromal cells in culture using confocal microscopy, zymography, immunoblots, and real-time polymerase chain reaction. In normal cornea EMMPRIN was predominantly expressed in the epithelium but was markedly induced in the anterior stroma of ulcerated corneas. This coincided with MMP-2 induction that co-localized with EMMPRIN at the epithelio-stromal boundary. The role of epithelial-stromal interaction in MMP induction was investigated in an in vitro co-culture system and demonstrated an induction and co-localization of EMMPRIN and MMP-2 in the fibroblasts at the interface with epithelial cells. Direct contact of fibroblasts with EMMPRIN-containing purified epithelial cell membranes also induced MMP-1, MMP-2, and EMMPRIN and this was inhibited by a blocking anti-EMMPRIN antibody, suggesting that EMMPRIN was primarily responsible for this induction. These findings, and the up-regulation of EMMPRIN by epidermal growth factor and transforming growth factor-beta, demonstrate a role for EMMPRIN in wound healing and suggest that sustained local up-regulation of EMMPRIN and MMPs in chronic situations in which healing is delayed may lead to excessive matrix degradation and corneal melts. 相似文献
77.
78.
Coindre JM Hostein I Maire G Derré J Guillou L Leroux A Ghnassia JP Collin F Pedeutour F Aurias A 《The Journal of pathology》2004,203(3):822-830
Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas. 相似文献
79.
Colland F Jacq X Trouplin V Mougin C Groizeleau C Hamburger A Meil A Wojcik J Legrain P Gauthier JM 《Genome research》2004,14(7):1324-1332
Access to the human genome facilitates extensive functional proteomics studies. Here, we present an integrated approach combining large-scale protein interaction mapping, exploration of the interaction network, and cellular functional assays performed on newly identified proteins involved in a human signaling pathway. As a proof of principle, we studied the Smad signaling system, which is regulated by members of the transforming growth factor beta (TGFbeta) superfamily. We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins, 179 of which were poorly or not annotated. The exploration of such complex interaction databases is improved by the use of PIMRider, a dedicated navigation tool accessible through the Web. The biological meaning of this network is illustrated by the presence of 18 known Smad-associated proteins. Functional assays performed in mammalian cells including siRNA knock-down experiments identified eight novel proteins involved in Smad signaling, thus validating this integrated functional proteomics approach. 相似文献
80.
Vincent Thomas-de-Montpréville Rémi Nottin Elisabeth Dulmet Alain Serraf 《Cardiovascular pathology》2007,16(1):22-28
BACKGROUND: Heart tumors are rare lesions with variegated histological types. Their clinicopathological features could be more comprehensively categorized. METHODS: This is a 19-year retrospective study of 17 infants/toddlers (<2 years of age) and 42 patients aged between 14 and 79 years (mean = 51.5) in a surgical center. RESULTS: Congenital tumors (n = 17; 29%), including rhabdomyomas (n = 9), ventricular fibromas (n = 6), and hemangiomas (n = 1), required surgery mainly because of mass effect. Familial myofibromatosis was the only embolic congenital lesion. Acquired benign tumors (n = 28; 47%) included myxomas (n = 21), fibroelastomas (n = 3), myofibroblastic inflammatory tumors (n = 2), and lipomas (n = 2). Eight (29%) were revealed by systemic embolization. These benign noncongenital tumors were all treated by complete resection, except for an incompletely resected lipoma of the mitral valve. Postoperative arrhythmia (n = 1) and pericardial effusion (n = 3) were the only complications. Primary sarcomas (n = 8; 14%) were mostly vascular tumors (five of eight), and patients with high-grade tumors had a mean survival of 15 months (n = 5). Cardiac metastases (n = 6; 10%) were from carcinomas (n = 3) or sarcomas (n = 3); apart from a necrotic metastasis, all patients died (mean survival of 6 months). CONCLUSIONS: This study shows that, regardless of patients' age, heart tumors can be classified as: (a) congenital lesions, which are spontaneously nonprogressive or regressive lesions possibly requiring surgery mainly because of mass effect; (b) acquired benign tumors, which are lesions requiring surgery often because of embolization risk; and (c) primary and secondary malignant tumors, which are lesions with globally poor prognosis but with some indications for resection. 相似文献