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11.
Because organ transplantation is the preferred treatment for organ failure, the demand for human organs for transplantation is large and growing. From this demand, several fields based on new technologies for the replacement or repair of damaged tissues and organs have emerged. These fields include stem cell biology, cloning, tissue engineering and xenotransplantation. Here we evaluate the potential contribution of these to the devising of alternative approaches to organ replacement. We present our vision for the development of two structurally complex organs – the lung and the kidney – based on a 'fusion' of new and established technologies. 相似文献
12.
The oral LD50 of Crotalaria assamica, which contains mainly monocrotaline, was found to be 154 mg/kg in mice. Neither liver necrosis nor morbidity was demonstrated with Eupatorium extract at a dose level of 144 mg/kg, which was equivalent to the LD20 of Crotalaria. Pretreatment with phenobarbitone enhanced the toxicity of both plant extracts in mice. In in vitro studies, "metabolic pyrrole" was formed by incubating Eupatorium japonicum extracts with liver microsomes. The rate of "pyrrole" formation was similar to that of Crotalaria extract and pure monocrotaline alkaloid, but was much slower than retrorsine. The rate of N-oxide formation was, in descending order, retrorsine, Eupatorium japonicum and Crotalaria/monocrotaline. It is concluded that the alkaloid in Eupatorium species is metabolized to "pyrrole" and an N-oxide metabolite in the liver, but hepatotoxicity is much lower when compared with that caused by Crotalaria. 相似文献
13.
14.
Targeted gene disruption of murine CD7 总被引:2,自引:0,他引:2
CD7 is a 40 kDa type I transmembrane glycoprotein member of the Ig
superfamily. CD7 is a marker of mature human T cells and NK cells, and is
expressed early in their development. Cross-linking CD7 positively
modulates T cell and NK cell activity as measured by calcium fluxes,
expression of adhesion molecules, cytokine secretion and proliferation. CD7
associates directly with phosphoinositol 3'-kinase, and CD7 ligation
induces production of D-3 phosphoinositides and tyrosine phosphorylation.
Severe combined immunodeficiency has been associated with a lack of
lymphocyte surface CD7. The CD7 ligand is unknown. The murine CD7 homolog
is encoded by a single gene on chromosome 11. In order to characterize the
role of CD7 in lymphocyte development and function we have eliminated the
CD7 gene by targeted disruption. CD7- deficient mice display normal
histology of thymus and spleen, normal lymphocyte populations in primary
and secondary lymphoid tissues, and normal serum Ig levels. Specific
antibody responses after immunization with T-dependent and T-independent
antigens are equivalent in wild-type and CD7 knockout mice. CD7-deficient
lymphocytes respond normally to T cell mitogenic and allogeneic stimuli,
and display normal NK cell cytotoxicity.
相似文献
15.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
16.
Bone marrow-derived macrophages from normal and burned rats were cultured for one and four days in the presence of LPS, PHA, or opsonized zymosan as activators, and the supernatants were assayed for the inflammatory mediators TNF, IL-6, and PGE2 and the cells assayed for cytotoxicity. The macrophages responded differently to the various stimuli regarding cytotoxicity and the production of mediators, perhaps implicating the complement receptor CR1 in TNF production and the LPS receptor CD14 or the PHA lectin receptor in IL-6 and PGE2 production and for cytotoxicity. The response of the cells also depended on culture time and postburn time; in addition, macrophages from burned and unburned animals responded differently, depending on postburn day and the type of stimulus. TNF production was generally higher for one-day compared to four-day cultures (i.e., TNF was disappearing in the cultures), but IL-6 and PGE2 production was greater in four-day cultures. The results of this study suggest that thermal injury can contribute to the development of inflammatory and cytotoxic macrophages from bone marrow progenitor cells. 相似文献
17.
James D. Ogle J. Greg Noel Ambikaipakan Balasurbramaniam R. Michael Sramkoski Cora K. Ogle J. Wesley Alexander 《Inflammation》1990,14(2):185-194
Both recombinant IL-1 and - caused an upregulation of C3b receptors (CR1) on human neutrophils and caused a receptor-mediated enhancement of phagocytosis of C3b·IgG-coated microspheres by these leukocytes. The and forms of the recombinant cytokine were of comparable potency regarding CR1 upregulation, although both generally had less than 25% of the potency of FMLP in this respect. Recombinant IL-1 was slightly more potent than the form of the cytokine regarding phagocytosis of opsonized microspheres and, again, both forms were less potent than FMLP in causing an enhancement of phagocytosis by neutrophils. The synthetic noninflammatory immunostimulatory nonapeptide corresponding to residues 163–171 of IL-1 was completely inert with respect to upregulation of CR1 on neutrophils and the enhancement of phagocytosis by these cells. Thus this domain in the intact IL-1 molecule apparently is not involved in CR1 upregulation and the ensuing enhancement in phagocytosis by neutrophils, although it is apparently important in the immunostimulatory activity regarding the proliferation of lymphocytes. 相似文献
18.
Dou Q; Tarnuzzer RW; Williams RS; Schultz GS; Chegini N 《Molecular human reproduction》1997,3(11):1005-1014
19.
The effects of histamine on the spontaneous activity of the isolated human myometrium were studied. Both the frequency and force of contractions of the muscle strips were not significantly altered by histamine. The presence of either a histamine H1-or H2-receptor antagonist in the organ bath did not significantly change the responses of the uterine muscle to histamine. These findings suggest that histamine has negligible effects on the human myometrium, possibly due to the absence, or paucity, of histamine receptors. 相似文献
20.
Needle biopsy of renal allografts: comparison of two techniques 总被引:2,自引:0,他引:2
Bogan ML; Kopecky KK; Kraft JL; Holladay AO; Filo RS; Leapman SB; Thomalla JV 《Radiology》1990,174(1):273-275
Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications. 相似文献