全文获取类型
收费全文 | 13277篇 |
免费 | 698篇 |
国内免费 | 100篇 |
专业分类
耳鼻咽喉 | 88篇 |
儿科学 | 226篇 |
妇产科学 | 147篇 |
基础医学 | 2136篇 |
口腔科学 | 98篇 |
临床医学 | 1355篇 |
内科学 | 2940篇 |
皮肤病学 | 357篇 |
神经病学 | 1297篇 |
特种医学 | 529篇 |
外科学 | 2022篇 |
综合类 | 56篇 |
一般理论 | 2篇 |
预防医学 | 686篇 |
眼科学 | 215篇 |
药学 | 918篇 |
中国医学 | 40篇 |
肿瘤学 | 963篇 |
出版年
2023年 | 63篇 |
2022年 | 86篇 |
2021年 | 256篇 |
2020年 | 152篇 |
2019年 | 223篇 |
2018年 | 316篇 |
2017年 | 201篇 |
2016年 | 236篇 |
2015年 | 271篇 |
2014年 | 372篇 |
2013年 | 510篇 |
2012年 | 907篇 |
2011年 | 1024篇 |
2010年 | 606篇 |
2009年 | 534篇 |
2008年 | 872篇 |
2007年 | 1014篇 |
2006年 | 905篇 |
2005年 | 946篇 |
2004年 | 878篇 |
2003年 | 863篇 |
2002年 | 842篇 |
2001年 | 140篇 |
2000年 | 98篇 |
1999年 | 145篇 |
1998年 | 216篇 |
1997年 | 171篇 |
1996年 | 161篇 |
1995年 | 110篇 |
1994年 | 115篇 |
1993年 | 111篇 |
1992年 | 92篇 |
1991年 | 56篇 |
1990年 | 46篇 |
1989年 | 59篇 |
1988年 | 45篇 |
1987年 | 40篇 |
1986年 | 44篇 |
1985年 | 27篇 |
1984年 | 46篇 |
1983年 | 38篇 |
1982年 | 48篇 |
1981年 | 30篇 |
1980年 | 36篇 |
1979年 | 23篇 |
1978年 | 19篇 |
1977年 | 16篇 |
1976年 | 12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 15 毫秒
61.
Ultan F. Power Hélène Plotnicky-Gilquin Thierry Huss Alain Robert Michel Trudel Stefan Ståhl Mathias Uhlén Thien Ngoc Nguyen Hans Binz 《Virology》1997,230(2):155
A subunit approach to the development of a respiratory syncytial virus (RSV) vaccine was investigated. It involved the production, inEscherichia coli,of an RSV (Long) G protein fragment (G2Na) as a C-terminal fusion partner to an albumin binding region (BB) of streptococcal protein G. G2Na incorporated amino acid residues 130–230 and was specifically recognized by murine anti-RSV-A polyclonal serum. In mice, intraperitoneal immunization with BBG2Na induced high anti-RSV-A serum ELISA titers and low to moderate neutralization activity. The immune response induced by BBG2Na demonstrated a potent protective efficacy against upper and lower respiratory tract RSV-A infection. The immunogenicity and protective efficacy of BBG2Na was maintained for at least 47 and 48 weeks, respectively, and was as potent and durable as live RSV-A administered in a similar fashion. Intramuscular immunization of cotton rats with BBG2Na protected lungs from both homologous and heterologous virus challenge. In contrast to mice, however, cotton rat nasal tracts were not protected after BBG2Na immunization. Consistent with antibody-mediated protection, virus was cleared within 24 hr from the lungs of BBG2Na-immunized mice. The anti-RSV-A antibodies induced in mice were exclusively of the IgG1 isotype and were detected in the serum, lungs, and nasal tracts. Passive transfer of these antibodies prevented acute, and eliminated chronic, RSV-A lung infection in normal and immunodeficient mice, respectively, confirming that such antibodies are important and sufficient for BBG2Na-induced pulmonary protection. Our results clearly demonstrate that BBG2Na contains an important immunogenic domain of the RSV G protein. The prokaryotic origin of this protein indicates that glycosylation of the RSV G protein is not necessary for protective efficacy. Thus, BBG2Na has potential as an RSV subunit vaccine. 相似文献
62.
Clio Mamalaki Marianna Murdjeva Mauro Tolaini Trisha Norton Phillip Chandler Alain Townsend Elizabeth Simpson Dimitris Kioussis 《Clinical & developmental immunology》1995,4(4):299-315
Influenza nucleoprotein (NP)-specific T-cell receptor transgenic mice (F5) were crossed
with transgenic mice expressing the cognate antigenic protein under the control of the H-
2Kb promoter. Double-transgenic mice show negative selection of thymocytes at the
CD4+8+TCR10 to CD4+8+TCRhi transition stage. A few CD8 T cells, however, escape clonal
deletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels of
the transgenic receptor and upregulated levels of the CD44 memory marker. Such cells do
not proliferate upon exposure to antigen stimulation in vivo or ex vivo, however, they can
develop low but detectable levels of antigen-specific cytotoxic function after stimulation
in vitro in the presence of IL-2. 相似文献
63.
Liciano Contu Inceborg Deschamps Henri Lestradet Jacques Hors Michel Schmid Marc Busson Alain Benajam Aline Marcelli-Barge Jean Dausset 《Tissue antigens》1982,20(2):123-140
Fifty-three families with at least one IDD patient were genotyped for 5 markers of the HLA complex including Bf and DR. In 8 families one of the parents was also affected and in 12 families more than two children were diseased. In total, 76 patients were genotyped. Their haplotypes were compared with those of 106 unrelated controls (the parents of 53 genotyped families).
The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfFl, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature. 相似文献
- 1)
Three haplotypes or segments of them (A2, Cw3, B15, BfS, DR4; Aw30, Cw5, B18, BfF I, DR3; and Al, Cw7, B8, BfS, DR3) were found more frequently in IDD patients.
- 2)
Measured by the 6 formula, the association of the postulated IDD susceptibility gene was very strong with the D-end of two of these haplotypes: BfF1, DR3 and BfS, DR4. However, the association was weak with the DR3 of the haplotype Al, Cw7, B8, BfS, DR3.
- 3)
An excess of HLA-identical affected siblings was found.
- 4)
An excess of DR3/DR4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased.
The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfFl, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature. 相似文献
64.
Diedhiou A Genin P Terris B Sauvanet A Belghiti J Degott C 《Annales de pathologie》2002,22(2):134-136
Undifferentiated embryonal sarcoma of the liver is rare. It is usually observed in children and adolescents. We report one case of embryonal sarcoma of the liver arising in patient without any antecedent. The only symptom was right scapular pain. The liver scan showed a multicystic lesion suspicious for infectious origin or a tumor. Serologies for ecchinococcus, schistosomiasis and brucellosis were negative. The treatment was a right hepatectomy. On gross examination, the tumor was unencapsulated, multicystic and contained large areas of necrosis admixed with gelatinous areas. Microscopically, there were epithelioid and spindle tumor cells in a myxo?d stroma. Lipoblastic-like or rhabdomyoblastic-like, giant cells and PAS positive hyaline globules in the cell cytoplasm were present. The tumor cells expressed vimentin, cytokeratin (KL1), alpha-1-antitrypsin and smooth muscle actin. This observation shows that embryonal sarcoma of the liver may develop in adult patients and should be taken into consideration in any differential diagnosis of cystic hepatic tumor. 相似文献
65.
Listeria monocytogenes Stimulates Mucus Exocytosis in Cultured Human Polarized Mucosecreting Intestinal Cells through Action of Listeriolysin O 总被引:4,自引:0,他引:4 下载免费PDF全文
Marie-Hlne Coconnier Elyess Dlissi Myriam Robard Christian L. Laboisse Jean-Louis Gaillard Alain L. Servin 《Infection and immunity》1998,66(8):3673-3681
When the intracellular pathogen Listeria monocytogenes infects cultured human mucosecreting polarized HT29-MTX cells apically, it induces the stimulation of mucus exocytosis without cell entry. Using a set of isogenic mutants and purified listeriolysin O (LLO), we identified the L. monocytogenes thiol-activated exotoxin LLO as the agonist of mucus secretion. We demonstrated that the LLO-induced mucus exocytosis did not result from the LLO membrane-damaging activity. We found that LLO-induced mucus exocytosis is an event requiring the binding of LLO to a brush border-associated receptor and membrane oligomerization of the exotoxin. By a pharmacological approach, we demonstrated that no regulatory system or intracellular transducing signal known to be involved in control of mucin exocytosis was activated by LLO. Based on the present data, the stimulatory action of LLO on mucin exocytosis could be accounted for either by an unknown signaling system which remains to be determined or by direct action of LLO with the membrane vesicle components involved in the intracellular vesicular transport of mucins. 相似文献
66.
Morning to evening changes in the electrical and mechanical properties of human soleus motor units activated by H reflex and M wave 总被引:2,自引:0,他引:2
The aim of the present study was to compare the relative contribution of the soleus motor units (MUs) activated by H and M
waves to the plantar-flexion torque in the morning and in the evening. Twelve healthy male subjects (physical education students)
took part in this investigation. The electromechanical properties of the plantar flexor muscles were recorded at two different
times of day: between 06:00 and 08:00 h and between 17:00 and 19:00 h. Plantar-flexion torque and concomitant electromyographic
activity of soleus muscle were assessed under voluntary and evoked conditions. The results indicated a significant decrease
in maximal voluntary muscle torque of triceps surae and associated soleus EMG in the evening as compared with the morning.
The mean values of MVC ranged from 131.6±9.6 N m in the morning to 125.1±9.0 N m in the evening. Peak-to-peak values of soleus
H
max and M
max potentials were comparable in the morning and in the evening (2.97 vs 3.18 mV and 7.95 vs 7.44 mV for H
max and M
max, respectively). The H
max/M
max ratio was not modified between the two experimental test sessions (34.8 vs 41.3%). The peak amplitude of the twitch produced
by the H
max wave
decreased significantly. When estimating the mechanical contribution to
of the slowest and fastest-twitch MUs reflexively and directly activated, we observed that the contribution of the slowest
MUs did not change while those of the fastest decreased significantly in the evening. To conclude, a weaker reflex twitch
torque caused by higher fatigue state of the MUs directly activated by the M wave which accompanied H
max in the evening may be regarded as a possible explanation of the weaker plantar-flexion torque production in the evening. 相似文献
67.
Schleiermacher G Raynal V Janoueix-Lerosey I Combaret V Aurias A Delattre O 《Genes, chromosomes & cancer》2004,39(2):143-150
In neuroblastoma, the most frequent genetic alteration is gain of chromosome arm 17q, which arises from unbalanced translocations. To document these genetic events more precisely, we performed an extensive study of chromosome 17 breakpoints in 27 neuroblastoma cell lines by using a combination of fluorescence in situ hybridization mapping with BAC/PAC clones and allele analysis with polymorphic markers. All cases exhibited one or more unbalanced chromosome 17 translocations, and 15 distinct breakpoint regions could be mapped. This high variability indicates that gene fusion or disruption events are extremely unlikely to account for the underlying oncogenic role of these translocations. However, breakpoints were not randomly distributed, most of them mapping to the proximal part of 17q. As a result of translocations, all cell lines but one exhibited gain of the 53.5 Mb-->qter fragment, bordered proximally by the clone CTC-462L7. The most telomeric breakpoint, flanked by the clone RP11-443M10, defined the 70.9 Mb-->qter fragment as a region of additional gain. In addition to chromosome gains, loss of heterozygosity for the short arm of chromosome 17 was observed in close to half the cases. It was either related to a chromosome 17 monosomy or to a uniparental isodisomy. Finally, in cases with a single normal chromosome 17, we show that the parental origin of the translocated chromosome 17 can be either distinct or identical to that of the normal chromosome. Similarly, multiple translocations within the same cell line can either involve the same or different chromosome 17 homologues, indicating the likely absence of parental origin bias in the generation of these alterations. 相似文献
68.
Imai K Zhu Y Revy P Morio T Mizutani S Fischer A Nonoyama S Durandy A 《Clinical immunology (Orlando, Fla.)》2005,115(3):277-285
Autosomal recessive form of hyper-IgM syndrome type 2 (AR-HIGM2) is secondary to mutations affecting both alleles of AICDA gene encoding activation-induced cytidine deaminase, characterized by defects of immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) in most of the patients. We herein report the immunological phenotype of seven patients carrying a single heterozygous R190X mutation in AICDA. Variable defect in in vivo CSR inherited as an autosomal dominant (AD) trait strongly suggests that this heterozygous AICDA mutation causes HIGM (AD-HIGM2). In AD-HIGM2 B cells, CSR was consistently found impaired in vitro. However, in contrast to AR-HIGM2, the CSR-induced double-stranded DNA breaks in the switch region of IgM heavy chain gene were detected. The SHM frequency in V regions of IgM heavy chain gene in B cells was normal in all (but one patient). The characteristics of the AD-HIGM2 phenotype indicate that the AID C-terminal region may be involved in DNA repair machinery required for CSR. 相似文献
69.
Tournier JN Hellmann AQ Lesca G Jouan A Drouet E Mathieu J 《Journal of leukocyte biology》2003,73(4):493-501
Fever is one of the most frequent clinical signs encountered in pathology, especially with respect to infectious diseases. It is currently thought that the role of fever on immunity is limited to activation of innate immunity; however, its relevance to activation of adaptive immunity remains unclear. Dendritic cells (DCs) that behave as sentinels of the immune system provide an important bridge between innate and adaptive immunity. To highlight the role of fever on adaptive immunity, we exposed murine bone marrow-derived lipopolysaccharide (LPS)- or live bacteria-maturing DCs over a 3-h period to 37 degrees C or to fever-like thermal conditions (39 degrees C or 40 degrees C). At these three temperatures, we measured the kinetics of cytokine production and the ability of DCs to induce an allogeneic mixed lymphocyte reaction. Our results show that short exposure of DCs to temperatures of 39 degrees C or 40 degrees C differentially increased the secretion of interleukin (IL)-12p70 and decreased the secretion of IL-10 and tumor necrosis factor alpha by maturing DCs. These fever-like conditions induced a regulation of cytokine production at the single-cell level. In addition, short-term exposed LPS-maturing DCs to 39 degrees C induced a stronger reaction with allogeneic CD4(+) T cells than maturing DCs incubated at 37 degrees C. These results provide evidence that temperature regulates cytokine secretion and DC functions, both of which are of particular importance in bacterial diseases. 相似文献
70.
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