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661.
Crackower MA; Scherer SW; Rommens JM; Hui CC; Poorkaj P; Soder S; Cobben JM; Hudgins L; Evans JP; Tsui LC 《Human molecular genetics》1996,5(5):571-579
Split hand/split foot malformation (SHFM) is a heterogeneous limb
developmental disorder, characterized by missing digits and fusion of
remaining digits. An autosomal dominant form of this disorder (SHFM1) has
been mapped to 7q21.3-q22.1 on the basis of SHFM-associated chromosomal
rearrangements. Utilizing a YAC contig across this region, we have defined
a critical interval of 1.5 Mb by the analysis of six interstitial deletion
patients and mapped the translocation breakpoints of seven ectrodactyly
patients within the interval. To delineate the basic molecular defect
underlying SHFM, we have searched for candidate genes in a 500 kb region
containing five of the translocation breakpoints. Three genes were
identified, two genes of the Distal-less (dii) homeobox gene family, DLX5
and DLX6 and a novel gene, which we named DSS1. DSS1 is predicted to encode
a highly acidic polypeptide with no significant similarity to any known
proteins but 100% amino acid sequence identify with its murine homolog
(Dss1). Using RNA in situ hybridization analysis, we detected a
tissue-specific expression profile for Dss1 in limb bud, craniofacial
primordia and skin. A deficiency in expression of Dss1, DLX5 and/or DLX6
during development may explain the SHFM phenotypes.
相似文献
662.
Development, behaviour and temperament: a prospective study of infants conceived through in-vitro fertilization 总被引:6,自引:3,他引:6
Gibson FL; Ungerer JA; Leslie GI; Saunders DM; Tennant CC 《Human reproduction (Oxford, England)》1998,13(6):1727-1732
The development, behaviour and temperament of 65 singleton infants
conceived through in-vitro fertilization (IVF) and 63 matched controls were
compared at 1 year postpartum. Primiparous women were recruited during
pregnancy and their infants' development was assessed at 1 year. In
addition, test-taking behaviour was evaluated by an examiner using the
Bayley behaviour rating scale and mothers completed a behaviour problem
checklist and temperament scale. Mental, motor, speech and social
development were appropriate for age, with no significant group
differences. While receptive language development was in the normal range,
IVF infants scored lower than control infants. Across both groups, mothers
reported low levels of behaviour difficulty and mean temperament ratings
were in the general population range. There were no group differences in
observed test-taking behaviour. However, IVF mothers rated their children
at a higher level of behaviour difficulty and more reactive than the
ratings given by control mothers. Overall, singleton children conceived
through IVF demonstrate appropriate general development at 1 year of age.
The higher reported behaviour difficulty experienced by IVF mothers may
reflect their concerns about the well-being and adjustment of their child
during the first year.
相似文献
663.
Rein MS; Powell WL; Walters FC; Weremowicz S; Cantor RM; Barbieri RL; Morton CC 《Molecular human reproduction》1998,4(1):83-86
Uterine leiomyomata (myomas) are associated with a variety of
characteristic cytogenetic abnormalities. The significance of these
chromosomal aberrations in the pathobiology of myomas remains to be
determined. The present study investigated the relationship between myoma
cytogenetic abnormalities and size. A total of 114 myoma specimens were
obtained from 92 patients undergoing myomectomy or hysterectomy. The
maximum diameter of each myoma was measured and a portion of each myoma
obtained for cytogenetic analysis. Karyotypes were analysed and categorized
as normal, abnormal (non-mosaic) or mosaic. Cytogenetic analyses revealed
73 (64%) normal, 20 (18%) abnormal (non-mosaic), and 21 (18%) mosaic
karyotypes. Mean myoma diameter was 6.5+/-0.44 cm with a range of 0.4-27
cm. Differences between the mean myoma diameter of specimens with normal
versus abnormal karyotypes was determined by the Kruskal-Wallis test. The
mean myoma diameter among specimens with abnormal (non-mosaic) karyotypes
was significantly greater than myomas with normal karyotypes (10.2+/- 5.9
versus 5.9+/-4.2 cm; P < 0.001). The proportion of abnormal (non-
mosaic) karyotypes in myomas >6.5 cm was compared to myomas <6.5 cm
by chi2-analysis; myomas >6.5 cm demonstrated a significantly higher
proportion of abnormal (non-mosaic) karyotypes when compared to myomas
<6.5 cm (75 versus 34%; P < 0.02). In summary, a significant
relationship exists between clonal cytogenetic abnormalities and myoma
size, suggesting that chromosomal abnormalities associated with individual
myomas enhance myoma growth.
相似文献
664.
Prolactin (PRL) is an important immunoregulatory hormone secreted by the
anterior pituitary gland. Hyperprolactinaemia has been implicated in the
pathogenesis of systemic lupus erythematosus (SLE). However, clinical
studies regarding the PRL level and lupus disease activity have yielded
contradictory results. The aim of our present study was, therefore, to
re-evaluate the association of PRL level and disease activity in SLE by
analysing a larger patient cohort and following them up serially.
Seventy-two consecutive SLE patients were recruited and the serum PRL level
was measured at each visit. Our results showed that hyperprolactinaemia
(> 500 mIU/l) occurred in 35% (25/72) of the patients. A total of 72%
(18/25) of the hyperprolactinaemic patients had mild elevation (arbitrarily
defined as 500-800 mIU/l) of the level only. No correlation could be found
between the PRL level and various clinical and serological parameters of
lupus disease activity. On serial follow-up of 44 patients, again no
correlation between PRL and disease activity could be demonstrated. We
conclude that hyperprolactinaemia occurs in some patients with SLE, but the
serum level of PRL does not correlate with clinical or serological disease
activity and is not a reliable marker for disease monitoring. The mechanism
and pathoaetiological and clinical significance of hyperprolactinaemia in a
small subset of SLE patients remain unclear and a longer follow-up is
necessary.
相似文献
665.
Feasibility of Clinicians Aligning Health Care with Patient Priorities in Geriatrics Ambulatory Care
666.
In vivo administration of murine recombinant granulocyte/macrophage colony stimulating factor (rGM-CSF) was evaluated for effects on survival and engraftment in an allogeneic murine bone marrow transplantation (BMT) model involving T-cell depletion of donor marrow. The model provides a high incidence of graft failure/rejection. Recipients of continuous subcutaneous infusions of rGM-CSF had a significant survival advantage when compared with untreated controls. However, a significantly lower incidence of donor cell engraftment was noted. Hematological parameters were not substantially affected. When rGM-CSF was administered intraperitoneally (IP), twice daily injections closely approximated the effects of continuous infusion on survival. Single IP injections were without significant effects on survival or engraftment. These results demonstrate that prolonged frequent in vivo exposure to rGM-CSF can significantly improve survival but significantly decreases donor cell repopulation in recipients of T-cell- depleted histoincompatible marrow grafts. 相似文献
667.
Between 1949 and 1968, 1369 female patients received primary treatment for breast cancer in the Robert-R?ssle-Clinic of the Central Institute for Cancer Research of the Academy of Sciences of the GDR. Using a sequential procedure based on decision theory, the influence of menopause on prognosis of breast cancer was investigated in clinical stage I--III. The following rank order of negative prognostic signs was found in the 365 patients of 46-55 years age (5-year survival rate in braquets): skin involved beyond breast (0%); inflammatory type of cancer (0%); fixation of chest wall (0%); radiation treatment only (10%); tumor diameter in surgical specimen 5 cm and more (26%); tumor diameter 10+ cm by clinical examination (31%); skin ulceration (0%); axillary lymph nodes considered to contain growth (40%); menopause (59.7%). 85% of menstrating patients without these adverse prognostic signs survived for more than 5 years. Taking into consideration other observations, it is suggested that breast cancer before menopause is mostly oestrogen-dependent. When the ovary ceases to produce oestrogens in the next future, the cancer looses hormonal stimuli necessary for growth. This interpretation is in agreement with the observations that younger menstruating women show a definitely worse prognosis (5-year survival rate 55,8%). In controlled clinical trials, patients before and after menopause should be randomized separately. 相似文献
668.
Potassium uptake and release by human blood platelets 总被引:1,自引:0,他引:1
Thrombin is known to reduce the K+ content of human platelets, but the subcellular origin of the lost K+ is not known. The effect of aggregating agents on K+ release was studied in platelets labeled in plasma by preincubation with 42KCI. Platelets were separated from plasma by gel filtration through Sepharose 2B equilibrated with K+ - free Tyrode's buffer. Platelet K+ was 116nEq/10(8) platelets, of which 23% was found to be extracellular immediately after gel filtration. K+ influx was 65 nEq/10(8) platelets/hr at pH 7.5 and was more rapid at pH 7.9. About 70% of cell K+ exchanged with plasma in 4 hr with first- order kinetics, while a minor fraction of about 30% exchanged with a slower time course. This slowly exchanging fraction of platelet K+ was thought to arise from heterogeneity in the platelet population. Epinephrine and ADP aggregated gel-filtered platelets and released serotonin, but with loss of only 5%-10% of cell K+ and no beta- glucuronidase. In contrast, thrombin released up to 30% of platelet K+, whether aggregation occurred or was prevented by not stirring the cells. The specific activity of K+ released by all aggregating agents was identical to the specific activity of total platelet K+. Thrombin (0.01-0.2 NIH U/ml) released serotonin and also beta-glucuronidase (an enzyme of the alpha-granule), and there was a linear relation between release of K+ and this enzyme (r = 0.88). No lysis of platelets occurred, since lactic dehydrogenase was not detected. Pretreatment of platelets with aspirin in vitro inhibited thrombin-induced release of serotonin but had no effect on the loss of K+ or beta-glucuronidase. In contrast, the ingestion of aspirin by mouth inhibited the release of serotonin, beta-glucuronidase, and K+ by thrombin. The data suggested that the K+ loss induced by thrombin was primarily derived from release of alpha-granules and that these organelles contained about 20% of the total platelet K+ in a freely exchangeable and nonsequestered state. 相似文献
669.
Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy 总被引:1,自引:2,他引:1
Hussein KK; Dahlberg S; Head D; Waddell CC; Dabich L; Weick JK; Morrison F; Saiki JH; Metz E; Rivkin SE 《Blood》1989,73(1):57-63
The Southwest Oncology Group conducted a study of acute lymphoblastic leukemia (ALL) in adults over a 5-year period, testing the utility of the L-10M regimen initially described by the group from Memorial Sloan- Kettering Cancer Center. One hundred sixty-eight eligible patients were treated with this intensive combination chemotherapy regimen. One hundred fifteen (68%) achieved complete remission. With the current median follow-up time of 34.5 months, the median durations of remission, relapse-free survival, and overall survival were 22.9, 20.9, and 17.7 months, respectively. Only 35% of the patients over 50 years of age achieved a complete remission. Age was a significant prognostic factor for complete response, survival, relapse-free survival, and remission duration. In addition, a low initial WBC count was found to have a statistically significant association with longer remission duration. Responders between the ages of 20 and 49 years with WBC counts of less than 15,000 appear to have an exceptionally good prognosis. 相似文献
670.
Interferon-alpha alters spectrin organization in normal and leukemic human B lymphocytes 总被引:2,自引:0,他引:2
Interferon-alpha (IFN-alpha) regulates the growth, differentiation, and recirculation of normal and malignant B lymphocytes. In this report we examine the effects of IFN-alpha on the distribution of the cytoskeletal protein spectrin in peripheral blood B lymphocytes from normal donors and patients diagnosed with chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Exposure of normal and leukemic B cells to IFN-alpha in vitro was shown by immunofluorescence microscopy to cause a dose-dependent increase in the percentage of cells containing discrete focal accumulations of spectrin, ie, a single large aggregate or cap-like structure near the plasma membrane. Although the magnitude of this effect was variable among individual patient samples, in some experiments IFN-alpha induced a fourfold increase in the percentage of leukemic B cells exhibiting focal accumulations of spectrin. Spectrin reorganization induced by IFN-alpha was abrogated by the protein synthesis inhibitor cycloheximide. In addition, IFN-alpha increased the total cellular content of spectrin in B-CLL cells by approximately twofold to fourfold. Finally, a role for protein kinase C in mediating the effects of IFN-alpha on spectrin's organization is implicated by studies in which calphostin C inhibited the IFN-induced focal accumulation of spectrin. Taken together, these studies suggest that the immunomodulatory activities of IFN-alpha in normal and malignant B cells involve a change in the organization of the spectrin- based cytoskeleton. 相似文献