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排序方式: 共有809条查询结果,搜索用时 15 毫秒
31.
Christiane Steeg Arne Von Benin Hans-Willi Mittrücker Bernard Malissen Bernhard Fleischer 《European journal of immunology》1997,27(9):2233-2238
T lymphocytes can be activated via the T cell receptor (TCR) or by triggering through a number of other surface structures, including the CD2 co-receptor molecule. Signaling through the CD2 molecule was shown previously to be dependent on the TCR-associated ζ-chain. Here, we show that CD2-induced activation also functions in T cells which express ζ-chains lacking a functional immune-receptor tyrosine-based activation motif (ITAM). TCR-positive T cells that express only the transmembrane part of the ζ-chain protein and thus lack a functional ζ-derived ITAM readily produce interleukin (IL)-2 when cross-linked with CD2-specific monoclonal antibodies (mAb). TCR-negative T cell hybridomas expressing minimal receptors consisting of an extracellular CD25 and an intracellular ζ-chain-derived segment were effectively stimulated via CD2-specific mAb. For CD2-mediated co-stimulation of TCR-negative cells, two ζ-chain-derived ITAM were sufficient to induce IL-2 when the CD2 molecules were co-cross-linked with the chimeric CD25-ζ molecules. Taken together, our results show that CD2-induced signaling does not necessarily employ the ζ-chain in TCR-positive cells and that CD2-dependent co-stimulation in TCR-negative cells can be mediated via two functional ζ-chain-derived ITAM. 相似文献
32.
E Waanders H Venselaar RHM Te Morsche DB De Koning PS Kamath VE Torres S Somlo JPH Drenth 《Clinical genetics》2010,78(1):47-56
Waanders E, Venselaar H, te Morsche RHM, de Koning DB, Kamath PS, Torres VE, Somlo S, Drenth JPH. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63. Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein structure and function. We screened 464 subjects including 76 probands by direct sequencing or conformation‐sensitive capillary electrophoresis. We analyzed the effects of all known and novel mutations using a combination of splice site recognition, evolutionary conservation, secondary and tertiary structure predictions, Poly Phen , and p Mut and sift . We identified a total of 26 novel mutations in PRKCSH (n = 14) and SEC63 (n = 12), including four splice site mutations, eight insertions/ deletions, six non‐sense mutations, and eight missense mutations. Out of 48 PCLD mutations, 13 were predicted to affect splicing. Most mutations were located in highly conserved regions and homology modeling for two domains of Sec63p showed severe effects of the residue substitutions. In conclusion, we identified 26 novel mutations associated with PCLD and we provide in silico analysis in order to delineate the role of these mutations. 相似文献
33.
Wolenski M Cramer SO Ehrlich S Steeg C Grossschupff G Tenner-Racz K Racz P Fleischer B von Bonin A 《Medical microbiology and immunology》2003,192(4):189-192
CD83 is used as a marker for mature dendritic cells (DC) in man. We have developed a new monoclonal antibody (mAb), Michel-17, that specifically recognizes mouse CD83. We show that murine CD83 is expressed mainly on mature DC and on activated T cells. Histological analysis of serial spleen sections revealed a CD83 expression pattern resembling that of MIDC-8, a known murine DC marker molecule. In contrast to other costimulatory receptors, cross-linking of CD83 with the mAb Michel-17 on DC or T cells does not induce any activation signals. Our data describe for the first time the expression pattern of murine CD83, which is comparable to that of human CD83.The unique mAb Michel-17 will help to elucidate the biological functions of the CD83 molecule in more detail. 相似文献
34.
Herjan van der Steeg Jesse P. van Akkeren Saskia Houterman Rudi M. H. Roumen 《Intensive care medicine》2009,35(5):914-918
Objective To evaluate the efficacy of the urine column (UC) measurement compared to the intra-vesicular pressure (IVP) measurement as
an estimation of intra-abdominal pressure (IAP) in patients with IAP up to 30 mmHg.
Methods Fifteen patients undergoing a laparoscopic cholecystectomy were studied. All patients were catheterized. IVP measurements
were performed using a pressure transducer connected to the culture aspiration port. UC measurements were done by holding
up the tubing against a measuring rod. The symphysis pubis was used as the zero-reference. IAP was raised from 0 to 30 mmHg
using increments of 5 mmHg, during which first the IVP and then UC measurement series were recorded end-expiratory. Fifty
and 100 ml of saline were used as a priming volume.
Results The IVP and UC measurements showed a significant correlation with IAP. Comparing IVP and UC showed a correlation of 0.91 (p < 0.001) for 50 ml and 0.87 (p < 0.001) for 100 ml of saline as a priming volume. Using 50 ml of saline, UC was 0.68 mmHg higher than IVP (95% CI −7.21
to +5.85 mmHg). For 100 ml of saline, UC was 1.23 mmHg lower than IVP (95% CI −7.41 to +9.87 mmHg).
Conclusion UC measurement shows significant correlation to IVP measurement as an estimation of the IAP. Further study needs to be done
to conclude whether UC measurement is a reliable clinical alternative to IVP measurement. 相似文献
35.
HW Schytz T Wienecke PS Oturai J Olesen & M Ashina 《Cephalalgia : an international journal of headache》2009,29(2):258-268
The parasympathetic nervous system is likely to be involved in migraine pathogenesis. We hypothesized that the cholinomimetic agonist carbachol would induce headache and vasodilation of cephalic and radial arteries. Carbachol (3 µg/kg) or placebo was randomly infused into 12 healthy subjects in a double-blind crossover study. Headache was scored on a verbal rating scale from 0–10. Velocity in the middle cerebral artery (VMCA ) and diameter of the superficial temporal artery (STA) and radial artery (RA) were recorded. Nine participants developed headache after carbachol compared with three after placebo. The area under the curve for headache was increased after carbachol compared with placebo both during infusion (0–30 min) ( P = 0.042) and in the postinfusion period (30–90 min) ( P = 0.027). Carbachol infusion caused a drop in VMCA ( P = 0.003) and an increase in STA diameter ( P = 0.006), but no increase in the RA diameter ( P = 0.200). In conclusion, the study demonstrated that carbachol caused headache and dilation of cephalic arteries in healthy subjects. 相似文献
36.
Vivian Zabrenetzky Curtis C. Harris Patricia S. Steeg David D. Roberts 《International journal of cancer. Journal international du cancer》1994,59(2):191-195
Thrombospondin (TSP) is a member of a family of extracellular matrix glycoproteins that may participate in multiple aspects of the metastatic cascade. We report an inverse correlation of steady-state Thbs-1 mRNA and protein expression with malignant progression among murine melanoma and human lung and breast carcinoma cell lines. Murine K-1735 melanoma cell lines of low metastatic potential, including K-1735 lines transfected with the murine nm23-1 cDNA, expressed higher TSP levels than related highly metastatic lines. In a model system of lung carcinoma malignant progression, immortalized human bronchial epithelial cells expressed higher TSP levels than v-Ki-ras, v-Ha-ras or n-ras transfectants, which in turn expressed higher TSP levels than tumor-derived, more aggressive variants. Among 3 unrelated breast carcinoma cell lines, Thbs-1 steady-state mRNA levels were greater in the 2 nonmetastatic lines than the metastatic line. Our data show that malignant progression in some cell lines is associated with reduced TSP expression. The suppressive effects of nm23-1 transfection on metastatic potential are also associated with increased TSP expression; ras transfection, which results in increased tumorigenesis, is associated with decreased TSP expression. 相似文献
37.
Kroese ED; Dortant PM; van Steeg H; van Oostrom CT; van der Houven van Oordt CW; van Kranen HJ; de Vries A; Wester PW; van Kreijl CF 《Carcinogenesis》1997,18(5):975-980
E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to
their low spontaneous tumour incidence and their increased sensitivity
towards the lymphomagen ethylnitrosourea these mice may present an
interesting model for short-term carcinogenicity testing. Here, we report
on the further exploration of this transgenic mouse model with two
additional carcinogens known to have, among others, the
lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and
12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week
(by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a
dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1
mice during the observation period of 40 weeks. B[a]P also induced tumours
of the forestomach within this observation period, though at a lower
incidence and apparently equally effective in wildtype and transgenic mice.
TPA, on the other hand, was unable to induce lymphomas (or tumours in any
other organ) in either transgenic or wildtype animals within the
observation period of 44 weeks, when applied dermally at the maximum
tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular
analysis showed that B[a]P-induced lymphomas in transgenic mice were of
T-cell origin, 80% of which had elevated levels of c-myc expression. None
of the lymphomas had increased N-myc expression and mutation analysis of
the ras-gene family revealed a K-ras mutation in only one out of eight
tumours investigated. Also, none of the lymphomas showed aberrant
expression of p53 as determined by immunohistochemistry. It is concluded
that the E mu-pim-1 mouse model will not be very suitable for short-term
carcinogenicity testing in general: only genotoxic chemicals that have the
lymphohaematopoietic system as target for carcinogenesis in wild- type
mice, appear to be efficiently identified.
相似文献
38.
The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention. 相似文献
39.
40.
Metastatic disease remains a significant contributor to morbidity and mortality in patients with breast cancer. An improved molecular and biochemical understanding of the metastatic process is expected to fuel the development of new therapeutic approaches. The suppression of tumor metastasis, despite tumor cell expression of oncogenes and metastasis-promoting events, has become a diverse and fruitful field of investigation. Although many genetic events promote metastasis, several genes show relatively reduced expression levels in metastatic tumor cells in mouse model systems and in aggressive human tumors. Re-expression of a metastasis-suppressor gene in a metastatic tumor cell line results in a significant reduction in metastatic behavior in vivo with no effect on tumorigenicity. The known metastasis-suppressor gene products nm23, KAI1, mitogen-activated protein kinase kinase 4, breast cancer metastasis suppressor-1, KiSS1, RHOGDI2, CRSP3, and vitamin D3-upregulated protein/thioredoxin interacting protein exhibit unexpected biochemical functions that have shed new light on signaling events that are important in metastasis. Most metastasis suppressors function at the translationally important stage of outgrowth of micrometastatic tumor cells at a distant site. We hypothesize that elevation of metastasis suppressor gene expression in micrometastatic tumor cells in the adjuvant high-risk population of patients with breast cancer will halt metastatic colonization and have a clinical benefit. DNA methylation inhibitors have shown limited promise in increasing metastasis-suppressor gene expression, and ligands of the nuclear hormone receptor family are currently under investigation in vitro and in vivo. Clinical testing of agents that increase metastasis-suppressor gene expression is expected to require tailored trial designs. 相似文献