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1.
Integrin stimulation regulates polymorphonuclear leukocytes inflammatory cytokine expression. 总被引:1,自引:0,他引:1 下载免费PDF全文
OBJECTIVE: The purpose of these studies is to investigate the role of integrin binding on the regulation of polymorphonuclear leukocyte (PMN) cytokine receptor expression. SUMMARY BACKGROUND DATA: Current knowledge in this area revolves around the ability of beta 2 integrins to mediate PMN adherence and chemotaxis. The role of alpha 1-6/beta 1 integrins in regulating cytokine receptor expression has not been probed. METHODS: Purified human PMN were adhered on plastic, fibronectin, or laminin-coated surfaces followed by the addition of iodine 125 (125I) monoclonal antibodies (mAbs) directed against tumor necrosis factor-alpha R (TNF-alpha R) p60, p80, or interleukin-1 beta R (IL-1 beta R) types I, II. Receptor expression was calculated based on the counts per minute (cpm) bound. The role of individual beta 1 integrins was assessed using mAbs directed against the alpha 1-6 subunit of the beta 1 complex, and integrin cross-linkage was achieved using secondary goat antimouse F(ab')2 antibodies. Polymorphonuclear leukocytes were pretreated with herbimycin A to determine the role of protein tyrosine kinase in mediating the effect of the beta 1 integrins. RESULTS: Adherence of PMN to Ln decreased IL-1 beta types I, II receptor expression, whereas adherence to Fn increased TNF-alpha R p60 and p80 expression. Anti-VLA-5 (CD49e) but not anti-VLA-1 through VLA-4 and VLA-6, blocked the effect of Fn on TNF-alpha receptors, whereas anti-VLA-6 but not anti-VLA-1 through VLA-5 blocked the effect of Ln on IL-1 beta receptors. Modulation of IL-1 beta and TNF-alpha receptors by VLA-5 and VLA-6 required protein tyrosine kinase activation as herbimycin A (10 micrograms/mL) blocked the affect of Fn and Ln. Changes in PMN cytokine receptor expression led to parallel changes in functional activity as assessed by the binding of 125I IL-1 beta and TNF-alpha. CONCLUSIONS: Integrin stimulation regulates the cell surface expression of PMN cytokine receptors. Ligation of CD49e upregulates TNF-alpha receptor expression, whereas binding of CD49f downregulates IL-1 beta receptor expression. Both processes are protein tyrosine kinase dependent. Changes in PMN cytokine receptor expression led to corresponding changes in functional activity. These results provide the first demonstration that chemotaxis of PMN into the interstitium provides a mechanism for ongoing participation in the local inflammatory response and is regulated by matrix protein integrin receptors. 相似文献
2.
This exploratory study has examined the effect of selected characteristics on the career advancement patterns of nurse executives in service and educational settings. The findings are not consistently in agreement with those of other researchers. For example, Hall et al. found that nearly two-thirds of nursing deans had planned their careers to attain that position. In this study, however, eighty-three percent of the respondents indicated that they had not planned their career advancement, but had simply taken opportunities that had come their way. The influence of others was important in the career advancement of these administrators. Many individuals, including faculty and nursing service colleagues, nursing directors, deans, and non-nursing administrators supported the respondents' personal and professional development through role modeling, teaching skills, and encouragement. Deliberate career planning and education in administration were, for the most part, lacking. Although the sample is too small to generate general conclusions about the universe of nurse executives, this does suggest that it is not uncommon for deans and service administrators to learn necessary skills on the job. 相似文献
3.
This paper describes a case of recurrent aorto-duodenal fistula treated successfully by re-sitting the duodenum in an ante-colic position. Secondary aorto-duodenal fistula affects less than 1% of patients who have received a prosthetic abdominal aortic graft. However following correction of such a fistula the incidence of recurrent fistulation or aortic stump blow-out is reported as high as 47%. we describe an alternative approach to management of this difficult problem. 相似文献
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Competitive control of the self-renewing T cell repertoire 总被引:1,自引:0,他引:1
We develop a mathematical model for the self-renewing part of the T cell
repertoire. Assuming that self-renewing T cells have to be stimulated by
immunogenic MHC-peptide complexes presented on the surfaces of
antigen-presenting cells, we derive a model of T cell growth in which
competition for MHC-peptide complexes limits T cell clone sizes and
regulates the total number of self-renewing T cells in the animal. We show
that for a sufficient diversity and/or degree of cross-reactivity, the
total T cell number hardly depends upon the diversity of the T cell
repertoire or the diversity of the set of presented peptides. Conversely,
for repertoires of lower diversity and/or cross-reactivity, steady-state
total T cell numbers may be limited by the diversity of the T cells. This
provides a possible explanation for the limited repertoire expansion in
some, but not all, mouse T cell re-constitution experiments. We suggest
that the competitive interactions described by our model underlie the
normal T cells numbers observed in transgenic mice, germ-free mice and
various knockout mice.
相似文献
8.
Localization of a gene for otosclerosis to chromosome 15q25-q26 总被引:5,自引:0,他引:5
Tomek MS; Brown MR; Mani SR; Ramesh A; Srisailapathy CR; Coucke P; Zbar RI; Bell AM; McGuirt WT; Fukushima K; Willems PJ; Van Camp G; Smith RJ 《Human molecular genetics》1998,7(2):285-290
Among white adults otosclerosis is the single most common cause of hearing
impairment. Although the genetics of this disease are controversial, the
majority of studies indicate autosomal dominant inheritance with reduced
penetrance. We studied a large multi- generational family in which
otosclerosis has been inherited in an autosomal dominant pattern. Five of16
affected persons have surgically confirmed otosclerosis; the remaining nine
have a conductive hearing loss but have not undergone corrective surgery.
To locate the disease- causing gene we completed genetic linkage analysis
using short tandem repeat polymorphisms (STRPs) distributed over the entire
genome. Multipoint linkage analysis showed that only one genomic region, on
chromosome 15q, generated a lod score >2.0. Additional STRPs were typed
in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and
D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis
gene.
相似文献
9.
Immune responses in mice infected with lactic dehydrogenase virus. IV. Functional status of the macrophage during acute LDV infection. 下载免费PDF全文
Macrophages from uninfected and lactic dehydrogenase virus (LDV)-infected mice were compared with respect to the affinity and number of their Fc receptors for IgG2a; no differences were found regarding these parameters. When the uptake of DNP-BGG by macrophages from uninfected and acutely LDV-infected mice was compared, again no differences were observed. However, when the per cent membrane-bound DNP-BGG was determined as a function of time after antigen uptake in these two groups, more DNP-BGG was found membrane-bound on the macrophages from the LDV-infected mice, than on uninfected macrophages. In view of the fact that humoral immunity is enhanced during acute LDV infection, these data provide a positive correlation between increased retention of membrane-bound antigen and enhanced humoral immune responses. 相似文献
10.
IMPT1, an imprinted gene similar to polyspecific transporter and multi- drug resistance genes 总被引:5,自引:1,他引:5
Dao D; Frank D; Qian N; O'Keefe D; Vosatka RJ; Walsh CP; Tycko B 《Human molecular genetics》1998,7(4):597-608
Human chromosome 11p15.5 and distal mouse chromosome 7 include a
megabase-scale chromosomal domain with multiple genes subject to parental
imprinting. Here we describe mouse and human versions of a novel imprinted
gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a
predicted multi-membrane-spanning protein similar to bacterial and
eukaryotic polyspecific metabolite transporter and multi- drug resistance
pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues
with metabolite transport functions, including liver, kidney, intestine,
extra-embryonic membranes and placenta, and there is strongly preferential
expression of the maternal allele in various mouse tissues at fetal stages.
In post-natal tissues there is persistent expression, but the allelic bias
attenuates. An allelic expression bias is also observed in human fetal and
post-natal tissues, but there is significant interindividual variation and
rare somatic allele switching. The fact that Impt1 is relatively repressed
on the paternal allele, together with data from other imprinted genes,
allows a statistical conclusion that the primary effect of human chromosome
11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative
repression of genes on the paternal homolog. Dosage regulation of the
metabolite transporter gene(s) by imprinting might regulate placental and
fetal growth.
相似文献